Skip to main content
SpringerLink
Log in

Cancer Secretomes and Their Place in Supplementing Other Hallmarks of Cancer

  • Chapter
  • First Online:
Advancements of Mass Spectrometry in Biomedical Research

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 806))

Abstract

The secretome includes all macromolecules secreted by cells, in particular conditions at defined times, allowing cell–cell communication. Cancer cell secretomes that are altered compared to normal cells have shown significant potential for elucidating cancer biology. Proteins of secretomes are secreted by various secretory pathways and can be studied using different methods. Cancer secretomes seem to play an important role in known hallmarks of cancers such as excessive proliferation, reduced apoptosis, immune invasion, angioneogenesis, alteration in energy metabolism, and development of resistance against anti-cancer therapy [1, 2]. If a significant role of an altered secretome can be identified in cancer cells, using advanced mass spectrometry-based techniques, this may allow researchers to screen and characterize the secretome proteins involved in cancer progression and open up new opportunities to develop new therapies. We aim to elaborate upon recent advances in cancer cell secretome analysis using different proteomics techniques. In this review, we highlight the role of the altered secretome in contributing to already recognized and emerging hallmarks of cancer and we discuss new challenges in the field of secretome analysis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    CAS  Google Scholar 

  2. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    CAS  Google Scholar 

  3. Tjalsma H, Bolhuis A, Jongbloed JD, Bron S, van Dijl JM (2000) Signal peptide-dependent protein transport in Bacillus subtilis: a genome-based survey of the secretome. Microbiol Mol Biol Rev 64:515–547

    CAS  Google Scholar 

  4. Agrawal GK, Jwa NS, Lebrun MH, Job D, Rakwal R (2010) Plant secretome: unlocking secrets of the secreted proteins. Proteomics 10:799–827

    CAS  Google Scholar 

  5. Walter P, Gilmore R, Blobel G (1984) Protein translocation across the endoplasmic reticulum. Cell 38:5–8

    CAS  Google Scholar 

  6. Mellman I, Warren G (2000) The road taken: past and future foundations of membrane traffic. Cell 100:99–112

    CAS  Google Scholar 

  7. van Vliet C, Thomas EC, Merino-Trigo A, Teasdale RD, Gleeson PA (2003) Intracellular sorting and transport of proteins. Prog Biophys Mol Biol 83:1–45

    Google Scholar 

  8. Rabouille C, Malhotra V, Nickel W (2012) Diversity in unconventional protein secretion. J Cell Sci 125:5251–5255

    CAS  Google Scholar 

  9. Nickel W (2003) The mystery of nonclassical protein secretion. A current view on cargo proteins and potential export routes. Eur J Biochem 270:2109–2119

    CAS  Google Scholar 

  10. Nickel W, Rabouille C (2009) Mechanisms of regulated unconventional protein secretion. Nat Rev Mol Cell Biol 10:148–155

    CAS  Google Scholar 

  11. Zhang M, Schekman R (2013) Cell biology. Unconventional secretion, unconventional solutions. Science 340:559–561

    CAS  Google Scholar 

  12. Kalra H, Adda CG, Liem M, Ang CS, Mechler A, Simpson RJ, Hulett MD, Mathivanan S (2013) Comparative proteomics evaluation of plasma exosome isolation techniques and assessment of the stability of exosomes in normal human blood plasma. Proteomics 13:3354–3364

    CAS  Google Scholar 

  13. Ji H, Greening DW, Barnes TW, Lim JW, Tauro BJ, Rai A, Xu R, Adda C, Mathivanan S, Zhao W, Xue Y, Xu T, Zhu HJ, Simpson RJ (2013) Proteome profiling of exosomes derived from human primary and metastatic colorectal cancer cells reveal differential expression of key metastatic factors and signal transduction components. Proteomics 13:1672–1686

    CAS  Google Scholar 

  14. Cocucci E, Racchetti G, Meldolesi J (2009) Shedding microvesicles: artefacts no more. Trends Cell Biol 19:43–51

    CAS  Google Scholar 

  15. Fevrier B, Vilette D, Archer F, Loew D, Faigle W, Vidal M, Laude H, Raposo G (2004) Cells release prions in association with exosomes. Proc Natl Acad Sci U S A 101:9683–9688

    CAS  Google Scholar 

  16. Azmi AS, Bao B, Sarkar FH (2013) Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review. Cancer Metastasis Rev 32(3–4):623–642

    CAS  Google Scholar 

  17. Akers JC, Gonda D, Kim R, Carter BS, Chen CC (2013) Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J Neurooncol 113:1–11

    Google Scholar 

  18. Dinter A, Berger EG (1998) Golgi-disturbing agents. Histochem Cell Biol 109:571–590

    CAS  Google Scholar 

  19. Chirico WJ (2011) Protein release through nonlethal oncotic pores as an alternative nonclassical secretory pathway. BMC Cell Biol 12:46

    CAS  Google Scholar 

  20. Huang CM, Nakatsuji T, Liu YT, Shi Y (2008) In vivo tumor secretion probing via ultrafiltration and tissue chamber: implication for anti-cancer drugs targeting secretome. Recent Pat Anticancer Drug Discov 3:48–54

    CAS  Google Scholar 

  21. Chiu KH, Chang YH, Liao PC (2013) Secretome analysis using a hollow fiber culture system for cancer biomarker discovery. Biochim Biophys Acta 1834:2285–2292

    CAS  Google Scholar 

  22. Pavlou MP, Kulasingam V, Sauter ER, Kliethermes B, Diamandis EP (2010) Nipple aspirate fluid proteome of healthy females and patients with breast cancer. Clin Chem 56:848–855

    CAS  Google Scholar 

  23. Hermanson M, Funa K, Hartman M, Claesson-Welsh L, Heldin CH, Westermark B, Nister M (1992) Platelet-derived growth factor and its receptors in human glioma tissue: expression of messenger RNA and protein suggests the presence of autocrine and paracrine loops. Cancer Res 52:3213–3219

    CAS  Google Scholar 

  24. Engebraaten O, Bjerkvig R, Pedersen PH, Laerum OD (1993) Effects of EGF, bFGF, NGF and PDGF(bb) on cell proliferative, migratory and invasive capacities of human brain-tumour biopsies in vitro. Int J Cancer 53:209–214

    CAS  Google Scholar 

  25. Pantazis P, Pelicci PG, Dalla-Favera R, Antoniades HN (1985) Synthesis and secretion of proteins resembling platelet-derived growth factor by human glioblastoma and fibrosarcoma cells in culture. Proc Natl Acad Sci U S A 82:2404–2408

    CAS  Google Scholar 

  26. Plate KH, Breier G, Farrell CL, Risau W (1992) Platelet-derived growth factor receptor-beta is induced during tumor development and upregulated during tumor progression in endothelial cells in human gliomas. Lab Invest 67:529–534

    CAS  Google Scholar 

  27. Lowe SW, Lin AW (2000) Apoptosis in cancer. Carcinogenesis 21:485–495

    CAS  Google Scholar 

  28. Falcon BL, Pietras K, Chou J, Chen D, Sennino B, Hanahan D, McDonald DM (2011) Increased vascular delivery and efficacy of chemotherapy after inhibition of platelet-derived growth factor-B. Am J Pathol 178:2920–2930

    CAS  Google Scholar 

  29. Warburg O, Posener K, Negelein E (1930) Ueber den Stoffwechsel der Tumoren. Biochem Z 152:319–344

    Google Scholar 

  30. Dang CV (2012) Links between metabolism and cancer. Genes Dev 26:877–890

    CAS  Google Scholar 

  31. Ehrlich P (1909) Über den jetzigen stand der karzinomforschung. Ned Tijdschr Geneeskd 5:273–290

    Google Scholar 

  32. Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD (2002) Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3:991–998

    CAS  Google Scholar 

  33. Shields JD, Kourtis IC, Tomei AA, Roberts JM, Swartz MA (2010) Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21. Science 328:749–752

    CAS  Google Scholar 

  34. Yang L, Pang Y, Moses HL (2010) TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression. Trends Immunol 31:220–227

    CAS  Google Scholar 

  35. Kim R, Emi M, Tanabe K (2006) Cancer immunosuppression and autoimmune disease: beyond immunosuppressive networks for tumour immunity. Immunology 119:254–264

    CAS  Google Scholar 

  36. Rabinovich GA, Gabrilovich D, Sotomayor EM (2007) Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol 25:267–296

    CAS  Google Scholar 

  37. Tredan O, Galmarini CM, Patel K, Tannock IF (2007) Drug resistance and the solid tumor microenvironment. J Natl Cancer Inst 99:1441–1454

    CAS  Google Scholar 

  38. Harbinski F, Craig VJ, Sanghavi S, Jeffery D, Liu L, Sheppard KA, Wagner S, Stamm C, Buness A, Chatenay-Rivauday C, Yao Y, He F, Lu CX, Guagnano V, Metz T, Finan PM, Hofmann F, Sellers WR, Porter JA, Myer VE, Graus-Porta D, Wilson CJ, Buckler A, Tiedt R (2012) Rescue screens with secreted proteins reveal compensatory potential of receptor tyrosine kinases in driving cancer growth. Cancer Discov 2:948–959

    CAS  Google Scholar 

  39. Yao L, Zhang Y, Chen K, Hu X, Xu LX (2011) Discovery of IL-18 as a novel secreted protein contributing to doxorubicin resistance by comparative secretome analysis of MCF-7 and MCF-7/Dox. PLoS One 6:e24684

    CAS  Google Scholar 

  40. Takata T, Ishigaki Y, Shimasaki T, Tsuchida H, Motoo Y, Hayashi A, Tomosugi N (2012) Characterization of proteins secreted by pancreatic cancer cells with anticancer drug treatment in vitro. Oncol Rep 28:1968–1976

    CAS  Google Scholar 

  41. Straussman R, Morikawa T, Shee K, Barzily-Rokni M, Qian ZR, Du J, Davis A, Mongare MM, Gould J, Frederick DT, Cooper ZA, Chapman PB, Solit DB, Ribas A, Lo RS, Flaherty KT, Ogino S, Wargo JA, Golub TR (2012) Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature 487:500–504

    CAS  Google Scholar 

  42. Wilson TR, Fridlyand J, Yan Y, Penuel E, Burton L, Chan E, Peng J, Lin E, Wang Y, Sosman J, Ribas A, Li J, Moffat J, Sutherlin DP, Koeppen H, Merchant M, Neve R, Settleman J (2012) Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. Nature 487:505–509

    CAS  Google Scholar 

  43. Fialkow PJ, Gartler SM, Yoshida A (1967) Clonal origin of chronic myelocytic leukemia in man. Proc Natl Acad Sci U S A 58:1468–1471

    CAS  Google Scholar 

  44. Clarkson B, Rubinow SI (1977) Growth kinetics in human leukemia. In: The University of Texas System Cancer Center M.D. Anderson Hospital and Tumor Institute 29th Annual Symposium on Fundamental Cancer Research, pp 592–627

    Google Scholar 

  45. Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737

    CAS  Google Scholar 

  46. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 100:3983–3988

    CAS  Google Scholar 

  47. Lang SH, Frame FM, Collins AT (2009) Prostate cancer stem cells. J Pathol 217:299–306

    CAS  Google Scholar 

  48. O’Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445:106–110

    Google Scholar 

  49. Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, Yan PS, Huang TH, Nephew KP (2008) Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 68:4311–4320

    CAS  Google Scholar 

  50. Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, Zhan Q, Jordan S, Duncan LM, Weishaupt C, Fuhlbrigge RC, Kupper TS, Sayegh MH, Frank MH (2008) Identification of cells initiating human melanomas. Nature 451:345–349

    CAS  Google Scholar 

  51. Rath BH, Fair JM, Jamal M, Camphausen K, Tofilon PJ (2013) Astrocytes enhance the invasion potential of glioblastoma stem-like cells. PLoS One 8:e54752

    CAS  Google Scholar 

  52. Emmink BL, Verheem A, Van Houdt WJ, Steller EJ, Govaert KM, Pham TV, Piersma SR, Borel Rinkes IH, Jimenez CR, Kranenburg O (2013) The secretome of colon cancer stem cells contains drug-metabolizing enzymes. J Proteomics 91:84–96

    CAS  Google Scholar 

  53. Skalnikova H, Motlik J, Gadher SJ, Kovarova H (2011) Mapping of the secretome of primary isolates of mammalian cells, stem cells and derived cell lines. Proteomics 11:691–708

    CAS  Google Scholar 

  54. Li H, Fan X, Houghton J (2007) Tumor microenvironment: the role of the tumor stroma in cancer. J Cell Biochem 101:805–815

    CAS  Google Scholar 

  55. Hanahan D, Coussens LM (2012) Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 21:309–322

    CAS  Google Scholar 

  56. Celis JE, Gromov P, Cabezon T, Moreira JM, Ambartsumian N, Sandelin K, Rank F, Gromova I (2004) Proteomic characterization of the interstitial fluid perfusing the breast tumor microenvironment: a novel resource for biomarker and therapeutic target discovery. Mol Cell Proteomics 3:327–344

    CAS  Google Scholar 

  57. Celis JE, Gromov P, Moreira JM, Cabezon T, Friis E, Vejborg IM, Proess G, Rank F, Gromova I (2006) Apocrine cysts of the breast: biomarkers, origin, enlargement, and relation with cancer phenotype. Mol Cell Proteomics 5:462–483

    CAS  Google Scholar 

  58. Celis JE, Moreira JM, Cabezon T, Gromov P, Friis E, Rank F, Gromova I (2005) Identification of extracellular and intracellular signaling components of the mammary adipose tissue and its interstitial fluid in high risk breast cancer patients: toward dissecting the molecular circuitry of epithelial-adipocyte stromal cell interactions. Mol Cell Proteomics 4:492–522

    CAS  Google Scholar 

  59. Karagiannis GS, Pavlou MP, Diamandis EP (2010) Cancer secretomics reveal pathophysiological pathways in cancer molecular oncology. Mol Oncol 4:496–510

    CAS  Google Scholar 

  60. Ngounou Wetie AG, Sokolowska I, Woods AG, Wormwood KL, Dao S, Patel S, Clarkson BD, Darie CC (2013) Automated mass spectrometry-based functional assay for the routine analysis of the secretome. J Lab Autom 18:19–29

    CAS  Google Scholar 

  61. Darie CC (2013) Mass spectrometry and its applications in life sciences. Aust J Chem 66:719–720

    CAS  Google Scholar 

  62. Ngounou Wetie AG, Sokolowska I, Woods AG, Roy U, Loo JA, Darie CC (2013) Investigation of stable and transient protein–protein interactions: past, present, and future. Proteomics 13:538–557

    CAS  Google Scholar 

  63. Sokolowska I, Wetie AGN, Woods AG, Darie CC (2013) Applications of mass spectrometry in proteomics. Aust J Chem 66:721–733

    CAS  Google Scholar 

  64. Ngounou Wetie AG, Sokolowska I, Woods AG, Darie CC (2013) Identification of post-translational modifications by mass spectrometry. Aust J Chem 66:734–748

    Google Scholar 

  65. Ngounou Wetie AG, Sokolowska I, Woods AG, Roy U, Deinhardt K, Darie CC (2014) Protein-protein interactions: switch from classical methods to proteomics and bioinformatics-based approaches. Cell Mol Life Sci 71(2):205–228

    CAS  Google Scholar 

  66. Sokolowska I, Gawinowicz MA, Ngounou Wetie AG, Darie CC (2012) Disulfide proteomics for identification of extracellular or secreted proteins. Electrophoresis 33:2527–2536

    CAS  Google Scholar 

  67. Sokolowska I, Ngounou Wetie AG, Roy U, Woods AG, Darie CC (2013) Mass spectrometry investigation of glycosylation on the NXS/T sites in recombinant glycoproteins. Biochim Biophys Acta 1834:1474–1483

    CAS  Google Scholar 

  68. Sokolowska I, Ngounou Wetie AG, Woods AG, Darie CC (2012) Automatic determination of disulfide bridges in proteins. J Lab Autom 17:408–416

    CAS  Google Scholar 

  69. Sokolowska I, Woods AG, Wagner J, Dorler J, Wormwood K, Thome J, Darie CC (2011) Mass spectrometry for proteomics-based investigation of oxidative stress and heat shock proteins. In: Andreescu S, Hepel M (eds) Oxidative stress: diagnostics, prevention, and therapy. American Chemical Society, Washington, DC

    Google Scholar 

  70. Woods AG, Ngounou Wetie AG, Sokolowska I, Russell S, Ryan JP, Michel TM, Thome J, Darie CC (2013) Mass spectrometry as a tool for studying autism spectrum disorder. J Mol Psychiatry 1:6

    Google Scholar 

  71. Woods AG, Sokolowska I, Darie CC (2012) Identification of consistent alkylation of cysteine-less peptides in a proteomics experiment. Biochem Biophys Res Commun 419:305–308

    CAS  Google Scholar 

  72. Woods AG, Sokolowska I, Yakubu R, Butkiewicz M, LaFleur M, Talbot C, Darie CC (2011) Blue native page and mass spectrometry as an approach for the investigation of stable and transient protein-protein interactions. In: Andreescu S, Hepel M (eds) Oxidative stress: diagnostics, prevention, and therapy. American Chemical Society, Washington, DC

    Google Scholar 

  73. Petrareanu C, Macovei A, Sokolowska I, Woods AG, Lazar C, Radu GL, Darie CC, Branza-Nichita N (2013) Comparative proteomics reveals novel components at the plasma membrane of differentiated HepaRG cells and different distribution in hepatocyte-and biliary-like cells. PLoS One 8:e71859

    CAS  Google Scholar 

  74. Sokolowska I, Dorobantu C, Woods AG, Macovei A, Branza-Nichita N, Darie CC (2012) Proteomic analysis of plasma membranes isolated from undifferentiated and differentiated HepaRG cells. Proteome Sci 10:47

    CAS  Google Scholar 

  75. Sokolowska I, Woods AG, Gawinowicz MA, Roy U, Darie CC (2012) Identification of a potential tumor differentiation factor receptor candidate in prostate cancer cells. FEBS J 279:2579–2594

    CAS  Google Scholar 

  76. Xiao T, Ying W, Li L, Hu Z, Ma Y, Jiao L, Ma J, Cai Y, Lin D, Guo S, Han N, Di X, Li M, Zhang D, Su K, Yuan J, Zheng H, Gao M, He J, Shi S, Li W, Xu N, Zhang H, Liu Y, Zhang K, Gao Y, Qian X, Cheng S (2005) An approach to studying lung cancer-related proteins in human blood. Mol Cell Proteomics 4:1480–1486

    CAS  Google Scholar 

  77. Pardo M, Garcia A, Antrobus R, Blanco MJ, Dwek RA, Zitzmann N (2007) Biomarker discovery from uveal melanoma secretomes: identification of gp100 and cathepsin D in patient serum. J Proteome Res 6:2802–2811

    CAS  Google Scholar 

  78. Xue H, Lu B, Lai M (2008) The cancer secretome: a reservoir of biomarkers. J Transl Med 6:52

    Google Scholar 

  79. Yao L, Lao W, Zhang Y, Tang X, Hu X, He C, Hu X, Xu LX (2012) Identification of EFEMP2 as a serum biomarker for the early detection of colorectal cancer with lectin affinity capture assisted secretome analysis of cultured fresh tissues. J Proteome Res 11(6):3281–3294

    CAS  Google Scholar 

  80. Stastna M, Van Eyk JE (2012) Investigating the secretome: lessons about the cells that comprise the heart. Circ Cardiovasc Genet 5:o8–o18

    Google Scholar 

  81. Stastna M, Van Eyk JE (2012) Secreted proteins as a fundamental source for biomarker discovery. Proteomics 12:722–735

    CAS  Google Scholar 

  82. Pavlou MP, Diamandis EP (2010) The cancer cell secretome: a good source for discovering biomarkers? J Proteomics 73:1896–1906

    CAS  Google Scholar 

  83. Caccia D, Dugo M, Callari M, Bongarzone I (2013) Bioinformatics tools for secretome analysis. Biochim Biophys Acta 1834:2442–2453

    CAS  Google Scholar 

  84. Emanuelsson O, Brunak S, von Heijne G, Nielsen H (2007) Locating proteins in the cell using TargetP, SignalP and related tools. Nat Protoc 2:953–971

    CAS  Google Scholar 

  85. Lawlor K, Nazarian A, Lacomis L, Tempst P, Villanueva J (2009) Pathway-based biomarker search by high-throughput proteomics profiling of secretomes. J Proteome Res 8:1489–1503

    CAS  Google Scholar 

  86. Mukherjee P, Mani S (2013) Methodologies to decipher the cell secretome. Biochim Biophys Acta 1834:2226–2232

    CAS  Google Scholar 

  87. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A (2003) The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res 13:2265–2270

    CAS  Google Scholar 

  88. Brown KJ, Formolo CA, Seol H, Marathi RL, Duguez S, An E, Pillai D, Nazarian J, Rood BR, Hathout Y (2012) Advances in the proteomic investigation of the cell secretome. Expert Rev Proteomics 9:337–345

    CAS  Google Scholar 

  89. Mbeunkui F, Fodstad O, Pannell LK (2006) Secretory protein enrichment and analysis: an optimized approach applied on cancer cell lines using 2D LC-MS/MS. J Proteome Res 5:899–906

    CAS  Google Scholar 

  90. Ge S, Mao Y, Yi Y, Xie D, Chen Z, Xiao Z (2012) Comparative proteomic analysis of secreted proteins from nasopharyngeal carcinoma-associated stromal fibroblasts and normal fibroblasts. Exp Ther Med 3:857–860

    CAS  Google Scholar 

  91. DeKroon RM, Osorio C, Robinette JB, Mocanu M, Winnik WM, Alzate O (2011) Simultaneous detection of changes in protein expression and oxidative modification as a function of age and APOE genotype. J Proteome Res 10:1632–1644

    CAS  Google Scholar 

  92. DeKroon RM, Robinette JB, Osorio C, Jeong JS, Hamlett E, Mocanu M, Alzate O (2012) Analysis of protein posttranslational modifications using DIGE-based proteomics. Methods Mol Biol 854:129–143

    CAS  Google Scholar 

  93. Winnik WM, Dekroon RM, Jeong JS, Mocanu M, Robinette JB, Osorio C, Dicheva NN, Hamlett E, Alzate O (2012) Analysis of proteins using DIGE and MALDI mass spectrometry. Methods Mol Biol 854:47–66

    CAS  Google Scholar 

  94. Jin L, Zhang Y, Li H, Yao L, Fu D, Yao X, Xu LX, Hu X, Hu G (2012) Differential secretome analysis reveals CST6 as a suppressor of breast cancer bone metastasis. Cell Res 22:1356–1373

    CAS  Google Scholar 

  95. Mauri P, Scarpa A, Nascimbeni AC, Benazzi L, Parmagnani E, Mafficini A, Della Peruta M, Bassi C, Miyazaki K, Sorio C (2005) Identification of proteins released by pancreatic cancer cells by multidimensional protein identification technology: a strategy for identification of novel cancer markers. FASEB J 19:1125–1127

    CAS  Google Scholar 

  96. Colangelo CM, Williams KR (2006) Isotope-coded affinity tags for protein quantification. Methods Mol Biol 328:151–158

    CAS  Google Scholar 

  97. Qu J, Jusko WJ, Straubinger RM (2006) Utility of cleavable isotope-coded affinity-tagged reagents for quantification of low-copy proteins induced by methylprednisolone using liquid chromatography/tandem mass spectrometry. Anal Chem 78:4543–4552

    CAS  Google Scholar 

  98. Yi EC, Li XJ, Cooke K, Lee H, Raught B, Page A, Aneliunas V, Hieter P, Goodlett DR, Aebersold R (2005) Increased quantitative proteome coverage with (13)C/(12)C-based, acid-cleavable isotope-coded affinity tag reagent and modified data acquisition scheme. Proteomics 5:380–387

    CAS  Google Scholar 

  99. Ong SE, Blagoev B, Kratchmarova I, Kristensen DB, Steen H, Pandey A, Mann M (2002) Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 1:376–386

    CAS  Google Scholar 

  100. Unwin RD, Griffiths JR, Whetton AD (2010) Simultaneous analysis of relative protein expression levels across multiple samples using iTRAQ isobaric tags with 2D nano LC-MS/MS. Nat Protoc 5:1574–1582

    CAS  Google Scholar 

  101. Hutchens TW, Yip TT (1993) New desorption strategies for the mass spectrometric analysis of macromolecules. Rapid Commun Mass Spectrom 7:576–580

    Google Scholar 

  102. Issaq HJ, Veenstra TD, Conrads TP, Felschow D (2002) The SELDI-TOF MS approach to proteomics: protein profiling and biomarker identification. Biochem Biophys Res Commun 292:587–592

    CAS  Google Scholar 

  103. Thirant C, Galan-Moya EM, Dubois LG, Pinte S, Chafey P, Broussard C, Varlet P, Devaux B, Soncin F, Gavard J, Junier MP, Chneiweiss H (2012) Differential proteomic analysis of human glioblastoma and neural stem cells reveals HDGF as a novel angiogenic secreted factor. Stem Cells 30:845–853

    CAS  Google Scholar 

  104. Tang CE, Guan YJ, Yi B, Li XH, Liang K, Zou HY, Yi H, Li MY, Zhang PF, Li C, Peng F, Chen ZC, Yao KT, Xiao ZQ (2010) Identification of the amyloid beta-protein precursor and cystatin C as novel epidermal growth factor receptor regulated secretory proteins in nasopharyngeal carcinoma by proteomics. J Proteome Res 9:6101–6111

    CAS  Google Scholar 

  105. Makridakis M, Roubelakis MG, Bitsika V, Dimuccio V, Samiotaki M, Kossida S, Panayotou G, Coleman J, Candiano G, Anagnou NP, Vlahou A (2010) Analysis of secreted proteins for the study of bladder cancer cell aggressiveness. J Proteome Res 9:3243–3259

    CAS  Google Scholar 

  106. Rondepierre F, Bouchon B, Bonnet M, Moins N, Chezal JM, D’Incan M, Degoul F (2010) B16 melanoma secretomes and in vitro invasiveness: syntenin as an invasion modulator. Melanoma Res 20:77–84

    CAS  Google Scholar 

  107. Gromov P, Gromova I, Bunkenborg J, Cabezon T, Moreira JM, Timmermans-Wielenga V, Roepstorff P, Rank F, Celis JE (2010) Up-regulated proteins in the fluid bathing the tumour cell microenvironment as potential serological markers for early detection of cancer of the breast. Mol Oncol 4:65–89

    CAS  Google Scholar 

  108. Shi HJ, Stubbs R, Hood K (2009) Characterization of de novo synthesized proteins released from human colorectal tumour explants. Electrophoresis 30:2442–2453

    CAS  Google Scholar 

  109. Volmer MW, Radacz Y, Hahn SA, Klein-Scory S, Stuhler K, Zapatka M, Schmiegel W, Meyer HE, Schwarte-Waldhoff I (2004) Tumor suppressor Smad4 mediates downregulation of the anti-adhesive invasion-promoting matricellular protein SPARC: Landscaping activity of Smad4 as revealed by a “secretome” analysis. Proteomics 4:1324–1334

    CAS  Google Scholar 

  110. Garcia-Lorenzo A, Rodriguez-Pineiro AM, Rodriguez-Berrocal FJ, Cadena MP, Martinez-Zorzano VS (2012) Changes on the Caco-2 secretome through differentiation analyzed by 2-D differential in-gel electrophoresis (DIGE). Int J Mol Sci 13:14401–14420

    CAS  Google Scholar 

  111. Yousefi Z, Sarvari J, Nakamura K, Kuramitsu Y, Ghaderi A, Mojtahedi Z (2012) Secretomic analysis of large cell lung cancer cell lines using two-dimensional gel electrophoresis coupled to mass spectrometry. Folia Histochem Cytobiol 50:368–374

    CAS  Google Scholar 

  112. Volmer MW, Stuhler K, Zapatka M, Schoneck A, Klein-Scory S, Schmiegel W, Meyer HE, Schwarte-Waldhoff I (2005) Differential proteome analysis of conditioned media to detect Smad4 regulated secreted biomarkers in colon cancer. Proteomics 5:2587–2601

    CAS  Google Scholar 

  113. Zeng X, Yang P, Chen B, Jin X, Liu Y, Zhao X, Liang S (2013) Quantitative secretome analysis reveals the interactions between epithelia and tumor cells by in vitro modulating colon cancer microenvironment. J Proteomics 89:51–70

    CAS  Google Scholar 

  114. Holmberg C, Ghesquiere B, Impens F, Gevaert K, Kumar JD, Cash N, Kandola S, Hegyi P, Wang TC, Dockray GJ, Varro A (2013) Mapping proteolytic processing in the secretome of gastric cancer-associated myofibroblasts reveals activation of MMP-1, MMP-2, and MMP-3. J Proteome Res 12:3413–3422

    CAS  Google Scholar 

  115. Barderas R, Mendes M, Torres S, Bartolome RA, Lopez-Lucendo M, Villar-Vazquez R, Pelaez-Garcia A, Fuente E, Bonilla F, Casal JI (2013) In-depth characterization of the secretome of colorectal cancer metastatic cells identifies key proteins in cell adhesion, migration, and invasion. Mol Cell Proteomics 12:1602–1620

    CAS  Google Scholar 

  116. Marimuthu A, Subbannayya Y, Sahasrabuddhe NA, Balakrishnan L, Syed N, Sekhar NR, Katte TV, Pinto SM, Srikanth SM, Kumar P, Pawar H, Kashyap MK, Maharudraiah J, Ashktorab H, Smoot DT, Ramaswamy G, Kumar RV, Cheng Y, Meltzer SJ, Roa JC, Chaerkady R, Prasad TS, Harsha HC, Chatterjee A, Pandey A (2013) SILAC-based quantitative proteomic analysis of gastric cancer secretome. Proteomics Clin Appl 7:355–366

    CAS  Google Scholar 

  117. Boersema PJ, Geiger T, Wisniewski JR, Mann M (2013) Quantification of the N-glycosylated secretome by super-SILAC during breast cancer progression and in human blood samples. Mol Cell Proteomics 12:158–171

    Google Scholar 

  118. Chen CY, Chi LM, Chi HC, Tsai MM, Tsai CY, Tseng YH, Lin YH, Chen WJ, Huang YH, Lin KH (2012) Stable isotope labeling with amino acids in cell culture (SILAC)-based quantitative proteomics study of a thyroid hormone-regulated secretome in human hepatoma cells. Mol Cell Proteomics 11(M111):011270

    Google Scholar 

  119. Formolo CA, Williams R, Gordish-Dressman H, MacDonald TJ, Lee NH, Hathout Y (2011) Secretome signature of invasive glioblastoma multiforme. J Proteome Res 10:3149–3159

    CAS  Google Scholar 

  120. Kashyap MK, Harsha HC, Renuse S, Pawar H, Sahasrabuddhe NA, Kim MS, Marimuthu A, Keerthikumar S, Muthusamy B, Kandasamy K, Subbannayya Y, Prasad TS, Mahmood R, Chaerkady R, Meltzer SJ, Kumar RV, Rustgi AK, Pandey A (2010) SILAC-based quantitative proteomic approach to identify potential biomarkers from the esophageal squamous cell carcinoma secretome. Cancer Biol Ther 10:796–810

    CAS  Google Scholar 

  121. Xu BJ, Yan W, Jovanovic B, An AQ, Cheng N, Aakre ME, Yi Y, Eng J, Link AJ, Moses HL (2010) Quantitative analysis of the secretome of TGF-beta signaling-deficient mammary fibroblasts. Proteomics 10:2458–2470

    CAS  Google Scholar 

  122. Gronborg M, Kristiansen TZ, Iwahori A, Chang R, Reddy R, Sato N, Molina H, Jensen ON, Hruban RH, Goggins MG, Maitra A, Pandey A (2006) Biomarker discovery from pancreatic cancer secretome using a differential proteomic approach. Mol Cell Proteomics 5:157–171

    CAS  Google Scholar 

  123. Chang YH, Lee SH, Chang HC, Tseng YL, Lai WW, Liao CC, Tsay YG, Liao PC (2012) Comparative secretome analyses using a hollow fiber culture system with label-free quantitative proteomics indicates the influence of PARK7 on cell proliferation and migration/invasion in lung adenocarcinoma. J Proteome Res 11:5167–5185

    CAS  Google Scholar 

  124. Chen HL, Seol H, Brown KJ, Gordish-Dressman H, Hill A, Gallo V, Packer R, Hathout Y (2012) Secretome survey of human plexiform neurofibroma derived Schwann cells reveals a secreted form of the RARRES1 protein. Int J Mol Sci 13:9380–9399

    CAS  Google Scholar 

  125. Choi DS, Choi DY, Hong BS, Jang SC, Kim DK, Lee J, Kim YK, Kim KP, Gho YS (2012) Quantitative proteomics of extracellular vesicles derived from human primary and metastatic colorectal cancer cells. J Extracell Vesicles:1–15, 18704

    Google Scholar 

  126. Schiarea S, Solinas G, Allavena P, Scigliuolo GM, Bagnati R, Fanelli R, Chiabrando C (2010) Secretome analysis of multiple pancreatic cancer cell lines reveals perturbations of key functional networks. J Proteome Res 9:4376–4392

    CAS  Google Scholar 

  127. Xue H, Lu B, Zhang J, Wu M, Huang Q, Wu Q, Sheng H, Wu D, Hu J, Lai M (2010) Identification of serum biomarkers for colorectal cancer metastasis using a differential secretome approach. J Proteome Res 9:545–555

    CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by The Enid A Haupt Charitable Trust, and The E./S. Sindina Lymphoma Research Fund, the MeadWestvaco Corp (to BDC). This work was also supported in part by the Keep a Breast Foundation (KEABF-375-35054), the David A. Walsh fellowship, and the U.S. Army research office (DURIP grant #W911NF-11-1-0304) (to CCD). CCD & AGNW would also like to thank Dr. Oscar Alzate, Dr. Robert M. Dekroon, and Ms. Mihaela Mocanu (Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC) for the initial steps in DIGE analysis.

Author information

Authors and Affiliations

  1. Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, 415 East 68th Street, New York, NY, 10065, USA

    Sapan Patel & Bayard D. Clarkson

  2. Biochemistry and Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University, 8 Clarkson Avenue, Postdam, NY, 13699-5810, USA

    Sapan Patel, Armand G. Ngounou Wetie & Costel C. Darie

  3. Molecular Pharmacology and Chemistry Program, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, 96, New York, NY, 10021, USA

    Bayard D. Clarkson

Authors
  1. Sapan Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Armand G. Ngounou Wetie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Costel C. Darie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bayard D. Clarkson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bayard D. Clarkson .

Editor information

Editors and Affiliations

  1. Chemistry and Biomolecular Science Biochemistry and Proteomics Group, Clarkson University, Potsdam, New York, USA

    Alisa G. Woods

  2. Chemistry and Biomolecular Science Biochemistry and Proteomics Group, Clarkson University, Potsdam, New York, USA

    Costel C. Darie

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Patel, S., Wetie, A.G.N., Darie, C.C., Clarkson, B.D. (2014). Cancer Secretomes and Their Place in Supplementing Other Hallmarks of Cancer. In: Woods, A., Darie, C. (eds) Advancements of Mass Spectrometry in Biomedical Research. Advances in Experimental Medicine and Biology, vol 806. Springer, Cham. https://doi.org/10.1007/978-3-319-06068-2_20

Download citation

Publish with us

Policies and ethics

Search

Navigation