Skip to main content
SpringerLink
Log in

DDRs in Healthy and Cancerous Reproductive Systems

  • Chapter
  • First Online:
Discoidin Domain Receptors in Health and Disease

  • 468 Accesses

Abstract

Discoidin domain receptors (DDRs) are uniquely positioned to function as sensors for extracellular matrix (ECM) and to regulate a wide range of cell functions from migration and proliferation to cytokine secretion and ECM homeostasis/remodeling. While activation of DDRs by ECM collagens is required for normal development and tissue homeostasis, aberrant activation and function of these receptors following injury or in disease is detrimental. Both DDRs are indicated to play key roles in development and metastasis of various types of cancer. In spite of this, the mechanisms whereby DDRs contribute to tumor formation and cancer progression are poorly understood. Among reproductive system cancers, epithelial ovarian cancer (EOC) and prostate cancer (PCa) result in high rates of morbidity and mortality. In EOC and PCa, atypical expressions of DDRs are indicated to function in malignancy and metastasis. The molecular mechanisms underlying how DDRs contribute to these and other pathologies need to be understood to find new markers and for development of therapeutic agents for treatment of disease. This is particularly the case for EOC in which mechanisms explaining the atypically high levels of DDR1 at initial and late stages of disease have not been described. We first outline studies showing an essential role for DDR2 in steroidogenesis and gamete development in ovary and testes. We then focus on what is known on the role of DDR1 and DDR2 in PCa and DDR1 in EOC. Finally, we speculate on possible functions DDR1 could be playing in different stages of EOC disease. Interactions between ECM proteins and cell surface receptors are well known to play key roles in regulation of cell behavior and determining physiological function. The switch from DDR2 expression in healthy ovaries to that of DDR1 in initial and late stages of EOC disease provides an experimental system to investigate to what extent ECM and DDR signaling enables malignant transformation.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover 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. Lemmon MA, Schlessinger J (2010) Cell signaling by receptor tyrosine kinases. Cell 141:1117–1134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Fu HL, Valiathan RR, Arkwright R, Sohail A, Mihai C, Kumarasiri M, Mahasenan KV, Mobashery S, Huang P, Agarwal G, Fridman R (2013) Discoidin domain receptors: unique receptor tyrosine kinases in collagen-mediated signaling. J Biol Chem 288:7430–7437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Alves F, Saupe S, Ledwon M, Schaub F, Hiddemann W, Vogel WF (2001) Identification of two novel, kinase-deficient variants of discoidin domain receptor 1: differential expression in human colon cancer cell lines. FASEB J 15:1321–1323

    CAS  PubMed  Google Scholar 

  4. Shrivastava A, Radziejewski C, Campbell E, Kovac L, McGlynn M, Ryan TE, Davis S, Goldfarb MP, Glass DJ, Lemke G, Yancopoulos GD (1997) An orphan receptor tyrosine kinase family whose members serve as nonintegrin collagen receptors. Mol Cell 1:25–34

    Article  CAS  PubMed  Google Scholar 

  5. Vogel W, Gish GD, Alves F, Pawson T (1997) The discoidin domain receptor tyrosine kinases are activated by collagen. Mol Cell 1:13–23

    Article  CAS  PubMed  Google Scholar 

  6. Kadler KE, Baldock C, Bella J, Boot-Handford RP (2007) Collagens at a glance. J Cell Sci 120:1955–1958

    Article  CAS  PubMed  Google Scholar 

  7. Hynes RO (2009) The extracellular matrix: not just pretty fibrils. Science 326:1216–1219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Heino J (2007) The collagen family members as cell adhesion proteins. Bioessays 29:1001–1010

    Article  CAS  PubMed  Google Scholar 

  9. Leitinger B, Hohenester E (2007) Mammalian collagen receptors. Matrix Biol 26:146–155

    Article  CAS  PubMed  Google Scholar 

  10. Leitinger B (2011) Transmembrane collagen receptors. Annu Rev Cell Dev Biol 27:265–290

    Article  CAS  PubMed  Google Scholar 

  11. Vogel W, Brakebusch C, Fassler R, Alves F, Ruggiero F, Pawson T (2000) Discoidin domain receptor 1 is activated independently of beta(1) integrin. J Biol Chem 275:5779–5784

    Article  CAS  PubMed  Google Scholar 

  12. Leitinger B, Kwan AP (2006) The discoidin domain receptor DDR2 is a receptor for type X collagen. Matrix Biol 25:355–364

    Article  CAS  PubMed  Google Scholar 

  13. Vogel WF, Abdulhussein R, Ford CE (2006) Sensing extracellular matrix: an update on discoidin domain receptor function. Cell Signal 18:1108–1116

    Article  CAS  PubMed  Google Scholar 

  14. Valiathan RR, Marco M, Leitinger B, Kleer CG, Fridman R (2012) Discoidin domain receptor tyrosine kinases: new players in cancer progression. Cancer Metastasis Rev 31:295–321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Borza CM, Pozzi A (2014) Discoidin domain receptors in disease. Matrix Biol 34:185–192

    Article  CAS  PubMed  Google Scholar 

  16. Olaso E, Labrador JP, Wang L, Ikeda K, Eng FJ, Klein R, Lovett DH, Lin HC, Friedman SL (2002) Discoidin domain receptor 2 regulates fibroblast proliferation and migration through the extracellular matrix in association with transcriptional activation of matrix metalloproteinase-2. J Biol Chem 277:3606–3613

    Article  CAS  PubMed  Google Scholar 

  17. Xu L, Peng H, Wu D, Hu K, Goldring MB, Olsen BR, Li Y (2005) Activation of the discoidin domain receptor 2 induces expression of matrix metalloproteinase 13 associated with osteoarthritis in mice. J Biol Chem 280:548–555

    Article  CAS  PubMed  Google Scholar 

  18. Kano K, Marín de Evsikova C, Young J, Wnek C, Maddatu TP, Nishina PM, Naggert JK (2008) A novel dwarfism with gonadal dysfunction due to loss-of-function allele of the collagen receptor gene, Ddr2, in the mouse. Mol Endocrinol 22:1866–1880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Snell GD (1929) Dwarf, a new Mendelian recessive character of the house mouse. Proc Natl Acad Sci U S A 15:733–734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Schaiber RH, Gowen JW (1961) A new dwarf mouse. Genetics 46:896

    Google Scholar 

  21. Bartke A (1964) Histology of the anterior hypophysis, thyroid and gonads of two types of dwarf mice. Anat Rec 149:225–235

    Article  CAS  PubMed  Google Scholar 

  22. Eicher EM, Beamer WG (1976) Inherited ateliotic dwarfism in mice: characteristics of the mutation, little, on chromosome 6. J Hered 67:87–91

    CAS  PubMed  Google Scholar 

  23. Matsumura H, Kano K, Marín de Evsikova C, Young JA, Nishina PM, Naggert JK, Naito K (2009) Transcriptome analysis reveals an unexpected role of a collagen tyrosine kinase receptor gene, Ddr2, as a regulator of ovarian function. Physiol Genomics 39:120–129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Berkholtz CB, Lai BE, Woodruff TK, Shea LD (2006) Distribution of extracellular matrix proteins type I collagen, type IV collagen, fibronectin, and laminin in mouse folliculogenesis. Histochem Cell Biol 126:583–592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Berkholtz CB, Shea LD, Woodruff TK (2006) Extracellular matrix functions in follicle maturation. Semin Reprod Med 24:262–269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kano K, Kitamura A, Matsuwaki T, Morimatsu M, Naito K (2010) Discoidin domain receptor 2 (DDR2) is required for maintenance of spermatogenesis in male mice. Mol Reprod Dev 77:29–37

    Article  CAS  PubMed  Google Scholar 

  27. Denmeade SR, Isaacs JT (2004) Development of prostate cancer treatment: the good news. Prostate 58:211–224

    Article  CAS  PubMed  Google Scholar 

  28. Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K (2000) Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343:78–85

    Article  CAS  PubMed  Google Scholar 

  29. Shimada K, Nakamura M, Ishida E, Higuchi T, Yamamoto H, Tsujikawa K, Konishi N (2008) Prostate cancer antigen-1 contributes to cell survival and invasion though discoidin receptor 1 in human prostate cancer. Cancer Sci 99:39–45

    CAS  PubMed  Google Scholar 

  30. Manolio TA (2010) Genomewide association studies and assessment of the risk of disease. N Engl J Med 363:166–176

    Article  CAS  PubMed  Google Scholar 

  31. Berndt SI, Sampson J, Yeager M, Jacobs KB, Wang Z et al (2011) Large-scale fine mapping of the HNF1B locus and prostate cancer risk. Hum Mol Genet 20:3322–3329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Gudmundsson J, Sulem P, Steinthorsdottir V, Bergthorsson JT et al (2007) Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nat Genet 39:977–983

    Article  CAS  PubMed  Google Scholar 

  33. Eeles RA, Kote-Jarai Z, Giles GG, Olama AA et al (2008) Multiple newly identified loci associated with prostate cancer susceptibility. Nat Genet 40:316–321

    Article  CAS  PubMed  Google Scholar 

  34. Thomas G, Jacobs KB, Yeager M, Kraft P et al (2008) Multiple loci identified in a genome-wide association study of prostate cancer. Nat Genet 40:310–315

    Article  CAS  PubMed  Google Scholar 

  35. Takata R, Akamatsu S, Kubo M, Takahashi A et al (2010) Genome-wide association study identifies five new susceptibility loci for prostate cancer in the Japanese population. Nat Genet 42:751–754

    Article  CAS  PubMed  Google Scholar 

  36. Liu F, Hsing AW, Wang X, Shao Q et al (2011) Systematic confirmation study of reported prostate cancer risk-associated single nucleotide polymorphisms in Chinese men. Cancer Sci 102:1916–1920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Sun J, Zheng SL, Wiklund F, Isaacs SD, Purcell LD, Gao Z, Hsu FC, Kim ST, Liu W, Zhu Y et al (2008) Evidence for two independent prostate cancer risk-associated loci in the HNF1B gene at 17q12. Nat Genet 40:1153–1155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bach I, Yaniv M (1993) More potent transcriptional activators or a transdominant inhibitor of the HNF1 homeoprotein family are generated by alternative RNA processing. EMBO J 12:4229–4242

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Kato N, Motoyama T (2009) Hepatocyte nuclear factor-1beta (HNF-1beta) in human urogenital organs: its expression and role in embryogenesis and tumorigenesis. Histol Histopathol 24:1479–1486

    CAS  PubMed  Google Scholar 

  40. Maestro MA, Cardalda C, Boj SF, Luco RF, Servitja JM, Ferrer J (2007) Distinct roles of HNF1beta, HNF1alpha, and HNF4alpha in regulating pancreas development, beta-cell function and growth. Endocr Dev 12:33–45

    Article  CAS  PubMed  Google Scholar 

  41. Glinsky GV, Glinskii AB, Stephenson AJ, Hoffman RM, Gerald WL (2004) Gene expression profiling predicts clinical outcome of prostate cancer. J Clin Invest 113:913–923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Buchner A, Castro M, Hennig A, Popp T, Assmann G, Stief CG, Zimmermann W (2010) Downregulation of HNF-1B in renal cell carcinoma is associated with tumor progression and poor prognosis. Urology 76:507–511

    Article  PubMed  Google Scholar 

  43. Harries LW, Perry JR, McCullag P, Crundwell M (2010) Alterations in LMTK2, MSMB and HNF1B gene expression are associated with the development of prostate cancer. BMC Cancer 10:315–326

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Hu YL, Zhong D, Pang F, Ning QY, Zhang YY, Li G, Wu JZ, Mo ZN (2013) HNF1b is involved in prostate cancer risk via modulating androgenic hormone effects and coordination with other genes. Genet Mol Res 12:1327–1335

    Article  CAS  PubMed  Google Scholar 

  45. Konishi N, Nakamura M, Ishida E, Shimada K, Mitsui E, Yoshikawa R, Yamamoto H, Tsujikawa K (2005) High expression of a new marker PCA-1 in human prostate carcinoma. Clin Cancer Res 11:5090–5097

    Article  CAS  PubMed  Google Scholar 

  46. Casimiro S, Guise TA, Chirgwin J (2009) The critical role of the bone microenvironment in cancer metastases. Mol Cell Endocrinol 310:71–81

    Article  CAS  PubMed  Google Scholar 

  47. Yoneda T (2011) Mechanism and strategy for treatment of cancer metastasis to bone. Gan To Kagaku Ryoho 38:877–884

    CAS  PubMed  Google Scholar 

  48. Juárez P, Guise TA (2011) TGF-β in cancer and bone: implications for treatment of bone metastases. Bone 48:23–29

    Article  PubMed  CAS  Google Scholar 

  49. Buijs JT, Juárez P, Guise TA (2011) Therapeutic strategies to target TGF-β in the treatment of bone metastases. Curr Pharm Biotechnol 12:2121–2137

    Article  CAS  PubMed  Google Scholar 

  50. Chen G, Deng C, Li Y-P (2012) TGF-β and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci 8:272–288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Soki FN, Park SI, McCauley LK (2012) The multifaceted actions of PTHrP in skeletal metastasis. Future Oncol 8:803–817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Isowa S, Shimo T, Ibaragi S, Kurio N, Okui T, Matsubara K, Hassan NM, Kishimoto K, Sasaki A (2010) PTHrP regulates angiogenesis and bone resorption via VEGF expression. Anticancer Res 30:2755–2767

    CAS  PubMed  Google Scholar 

  53. Liao J, Li X, Koh AJ, Berry JE, Thudi N, Rosol TJ, Pienta KJ, McCauley LK (2008) Tumor expressed PTHrP facilitates prostate cancer-induced osteoblastic lesions. Int J Cancer 123:2267–2278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Mak IW, Cowan RW, Turcotte RE, Singh G, Ghert M (2011) PTHrP induces autocrine/paracrine proliferation of bone tumor cells through inhibition of apoptosis. PLoS One 6, e19975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kremer R, Li J, Camirand A, Karaplis AC (2011) Parathyroid hormone related protein (PTHrP) in tumor progression. Adv Exp Med Biol 720:145–160

    Article  CAS  PubMed  Google Scholar 

  56. Rucci N, Teti A (2010) Osteomimicry: how tumor cells try to deceive the bone. Front Biosci (Schol Ed) 2:907–915

    Google Scholar 

  57. Pratap J, Lian JB, Javed A, Barnes GL, van Wijnen AJ, Stein JL, Stein GS (2006) Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone. Cancer Metastasis Rev 25:589–600

    Article  CAS  PubMed  Google Scholar 

  58. Akech J, Wixted JJ, Bedard K, van der Deen M, Hussain S, Guise TA, van Wijnen AJ, Stein JL, Languino LR, Altieri DC, Pratap J, Keller E, Stein GS, Lian JB (2010) Runx2 association with progression of prostate cancer in patients: mechanisms mediating bone osteolysis and osteoblastic metastatic lesions. Oncogene 29:811–821

    Article  CAS  PubMed  Google Scholar 

  59. Pratap J, Lian JB, Stein GS (2011) Metastatic bone disease: role of transcription factors and future targets. Bone 48:30–36

    Article  CAS  PubMed  Google Scholar 

  60. Baniwal SK, Khalid O, Gabet Y, Shah RR, Purcell DJ, Mav D, Kohn-Gabet AE, Shi Y, Coetzee GA, Frenkel B (2010) Runx2 transcriptome of prostate cancer cells: insights into invasiveness and bone metastasis. Mol Cancer 9:258–275

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Zhang Y, Jin S, Jiangtian Y, Xin B, Ren T, Yao L (2011) An essential role of discoidin domain receptor 2 (DDR2) in osteoblast differentiation and chondrocyte maturation via modulation of Runx2 activation. J Bone Miner Res 26:604–617

    Article  CAS  PubMed  Google Scholar 

  62. Lin KL, Chou CH, Hsieh SC, Hwa SY, Lee MT, Wang FF (2010) Transcriptional upregulation of DDR2 by ATF4 facilitates osteoblastic differentiation through p38 MAPK mediated Runx2 activation. J Bone Miner Res 25:2489–2503

    Article  CAS  PubMed  Google Scholar 

  63. Yan Z, Jin S, Wei Z, Huilian H, Zhanhai Y, Yue T, Juan L, Jing L, Libo Y, Xu L (2014) Discoidin domain receptor 2 facilitates prostate cancer bone metastasis via regulating parathyroid hormone-related protein. Biochim Biophys Acta 1842:1350–1363

    Article  CAS  PubMed  Google Scholar 

  64. Kim D, Ko P, You E, Rhee S (2014) The intracellular juxtamembrane domain of discoidin domain receptor 2 (DDR2) is essential for receptor activation and DDR2-mediated cancer progression. Int J Cancer 135:2547–2557

    Article  CAS  PubMed  Google Scholar 

  65. Laval S, Butler R, Shelling AN, Hanby AM, Poulsom R, Ganesan TS (1994) Isolation and characterization of an epithelial-specific receptor tyrosine kinase from an ovarian cancer cell line. Cell Growth Differ 5:1173–1183

    CAS  PubMed  Google Scholar 

  66. Shelling AN, Butler R, Jones T, Laval S, Boyle JM, Ganesan TS (1995) Localization of an epithelial-specific receptor kinase (EDDR1) to chromosome 6q16. Genomics 25:584–587

    Article  CAS  PubMed  Google Scholar 

  67. Heinzelmann-Schwarz VA, Gardiner-Garden M, Henshall SM, Scurry J, Scolyer RA, Davies MJ et al (2004) Overexpression of the cell adhesion molecules DDR1, Claudin 3, and Ep-CAM in metaplastic ovarian epithelium and ovarian cancer. Clin Cancer Res 10:4427–4436

    Article  CAS  PubMed  Google Scholar 

  68. Hansen C, Greengard P, Nairn AC, Andersson T, Vogel WF (2006) Phosphorylation of DARPP-32 regulates breast cancer cell migration downstream of the receptor tyrosine kinase DDR1. Exp Cell Res 312:4011–4018

    Article  CAS  PubMed  Google Scholar 

  69. Jonsson M, Andersson T (2001) Repression of Wnt-5a impairs DDR1 phosphorylation and modifies adhesion and migration of mammary cells. J Cell Sci 114:2043–2053

    CAS  PubMed  Google Scholar 

  70. Quan J, Yahata T, Adachi S, Yoshihara K, Tanaka K (2011) Identification of receptor tyrosine kinase, discoidin domain receptor 1 (DDR1), as a potential biomarker for serous ovarian cancer. Int J Mol Sci 12:971–982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Christofori G (2003) Changing neighbours, changing behaviour: cell adhesion molecule-mediated signalling during tumour progression. EMBO J 22:2318–2323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Vogel WF (2002) Ligand-induced shedding of discoidin domain receptor 1. FEBS Lett 514:175–180

    Article  CAS  PubMed  Google Scholar 

  73. Zhao G, Chen J, Deng Y, Gao F, Zhu J, Feng Z, Lv X, Zhao Z (2011) Identification of NDRG1-regulated genes associated with invasive potential in cervical and ovarian cancer cells. Biochem Biophys Res Commun 408:154–159

    Article  CAS  PubMed  Google Scholar 

  74. Colas E, Perez C, Cabrera S, Pedrola N, Monge M, Castellvi J et al (2011) Molecular markers of endometrial carcinoma detected in uterine aspirates. Int J Cancer 129:2435–2444

    Article  CAS  PubMed  Google Scholar 

  75. Domenyuk VP, Litovkin KV, Verbitskaya TG, Dubinina VG, Bubnov VV (2007) Identification of new DNA markers of endometrial cancer in patients from the Ukrainian population. Exp Oncol 29:152–155

    CAS  PubMed  Google Scholar 

  76. Rudd ML, Mohamed H, Price JC, O'Hara AJ, Le Gallo M, Urick ME, NISC Comparative Sequencing Program, Cruz P, Zhang S, Hansen NF, Godwin AK, Sgroi DC, Wolfsberg TG, Mullikin JC, Merino MJ, Bell DW (2014) Mutational analysis of the tyrosine kinome in serous and clear cell endometrial cancer uncovers rare somatic mutations in TNK2 and DDR1. BMC Cancer 26:884–892

    Article  CAS  Google Scholar 

  77. Lu Z, Wang J, Wientjes MG, Au JL (2010) Intraperitoneal therapy for peritoneal cancer. Future Oncol 6:1625–1641

    Article  PubMed  PubMed Central  Google Scholar 

  78. Sadeghi B, Arvieux C, Glehen O, Beaujard AC, Rivoire M, Baulieux J et al (2000) Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer 88:358–363

    Article  CAS  PubMed  Google Scholar 

  79. Karst AM, Drapkin R (2010) Ovarian cancer pathogenesis: a model in evolution. J Oncol 2010:932371

    Article  PubMed  CAS  Google Scholar 

  80. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62:10–29

    Article  PubMed  Google Scholar 

  81. Agarwal R, Kaye SB (2003) Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev Cancer 3:502–516

    Article  CAS  PubMed  Google Scholar 

  82. Chien JR, Aletti G, Bell DA, Keeney GL, Shridhar V, Hartmann LC (2007) Molecular pathogenesis and therapeutic targets in epithelial ovarian cancer. J Cell Biochem 102:1117–1129

    Article  CAS  PubMed  Google Scholar 

  83. Kucukmetin A, Naik R, Galaal K, Bryant A, Dickinson HO (2010) Palliative surgery versus medical management for bowel obstruction in ovarian cancer. Cochrane Database Syst Rev 7, CD007792

    PubMed  Google Scholar 

  84. Stratton JF, Tidy JA, Paterson ME (2001) The surgical management of ovarian cancer. Cancer Treat Rev 27:111–118

    Article  CAS  PubMed  Google Scholar 

  85. Tan DS, Agarwal R, Kaye SB (2006) Mechanisms of transcoelomic metastasis in ovarian cancer. Lancet Oncol 7:925–934

    Article  PubMed  Google Scholar 

  86. Deraco M, Baratti D, Laterza B, Balestra MR, Mingrone E, Macri A et al (2011) Advanced cytoreduction as surgical standard of care and hyperthermic intraperitoneal chemotherapy as promising treatment in epithelial ovarian cancer. Eur J Surg Oncol 37:4–9

    Article  CAS  PubMed  Google Scholar 

  87. Harmon RL, Sugarbaker PH (2005) Prognostic indicators in peritoneal carcinomatosis from gastrointestinal cancer. Int Semin Surg Oncol 2:3

    Article  PubMed  PubMed Central  Google Scholar 

  88. Sodek KL, Murphy KJ, Brown TJ, Ringuette MJ (2012) Cell–cell and cell–matrix dynamics in intraperitoneal cancer metastasis. Cancer Metastasis Rev 31:397–414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Mutsaers SE (2002) Mesothelial cells: their structure, function and role in serosal repair. Respirology 7:171–191

    Article  PubMed  Google Scholar 

  90. Witz CA, Montoya-Rodriguez IA, Cho S, Centonze VE, Bonewald LF, Schenken RS (2001) Composition of the extracellular matrix of the peritoneum. J Soc Gynecol Invest 8:299–304

    Article  CAS  Google Scholar 

  91. Rump A, Morikawa Y, Tanaka M, Minami S, Umesaki N, Takeuchi M et al (2004) Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion. J Biol Chem 279:9190–9198

    Article  CAS  PubMed  Google Scholar 

  92. Burleson KM, Casey RC, Skubitz KM, Pambuccian SE, Oegema TR Jr, Skubitz AP (2004) Ovarian carcinoma ascites spheroids adhere to extracellular matrix components and mesothelial cell monolayers. Gynecol Oncol 93:170–181

    Article  CAS  PubMed  Google Scholar 

  93. Burleson KM, Hansen LK, Skubitz AP (2004) Ovarian carcinoma spheroids disaggregate on type I collagen and invade live human mesothelial cell monolayers. Clin Exp Metastasis 21:685–697

    Article  CAS  PubMed  Google Scholar 

  94. Lessan K, Aguiar DJ, Oegema T, Siebenson L, Skubitz AP (1999) CD44 and beta1 integrin mediate ovarian carcinoma cell adhesion to peritoneal mesothelial cells. Am J Pathol 154:1525–1537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Casey RC, Burleson KM, Skubitz KM, Pambuccian SE, Oegema TR Jr, Ruff LE et al (2001) Beta 1-integrins regulate the formation and adhesion of ovarian carcinoma multicellular spheroids. Am J Pathol 159:2071–2080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Strobel T, Cannistra SA (1999) Beta1-integrins partly mediate binding of ovarian cancer cells to peritoneal mesothelium in vitro. Gynecol Oncol 73:362–367

    Article  CAS  PubMed  Google Scholar 

  97. Krist LF, Kerremans M, Broekhuis-Fluitsma DM, Eestermans IL, Meyer S, Beelen RH (1998) Milky spots in the greater omentum are predominant sites of local tumour cell proliferation and accumulation in the peritoneal cavity. Cancer Immunol Immunother 47:205–212

    Article  CAS  PubMed  Google Scholar 

  98. Mochizuki Y, Nakanishi H, Kodera Y, Ito S, Yamamura Y, Kato T et al (2004) TNF-alpha promotes progression of peritoneal metastasis as demonstrated using a green fluorescence protein (GFP)-tagged human gastric cancer cell line. Clin Exp Metastasis 21:39–47

    Article  CAS  PubMed  Google Scholar 

  99. Sorensen EW, Gerber SA, Sedlacek AL, Rybalko VY, Chan WM, Lord EM (2012) Omental immune aggregates and tumor metastasis within the peritoneal cavity. Immunol Res 45:185–194

    Article  CAS  Google Scholar 

  100. Tsujimoto H, Takhashi T, Hagiwara A, Shimotsuma M, Sakakura C, Osaki K et al (1995) Site-specific implantation in the milky spots of malignant cells in peritoneal dissemination: immunohistochemical observation in mice inoculated intraperitoneally with bromodeoxyuridine-labelled cells. Br J Cancer 71:468–472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Oosterling SJ, van der Bij GJ, Bogels M, van der Sijp JR, Beelen RH, Meijer S et al (2006) Insufficient ability of omental milky spots to prevent peritoneal tumor outgrowth supports omentectomy in minimal residual disease. Cancer Immunol Immunother 55:1043–1051

    Article  CAS  PubMed  Google Scholar 

  102. Stadlmann S, Raffeiner R, Amberger A, Margreiter R, Zeimet AG, Abendstein B et al (2003) Disruption of the integrity of human peritoneal mesothelium by interleukin-1beta and tumor necrosis factor-alpha. Virchows Arch 443:678–685

    Article  CAS  PubMed  Google Scholar 

  103. Allen M, Louise Jones J (2011) Jekyll and Hyde: the role of the microenvironment on the progression of cancer. J Pathol 223:162–176

    CAS  PubMed  Google Scholar 

  104. Swartz MA, Iida N, Roberts EW, Sangaletti S, Wong MH, Yull FE, Coussens LM, DeClerck YA (2012) Tumor microenvironment complexity: emerging roles in cancer therapy. Cancer Res 72:2473–2480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Finley SD, Popel AS (2013) Effect of tumor microenvironment on tumor VEGF during anti-VEGF treatment: systems biology predictions. J Natl Cancer Inst 105:802–811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Bhatt RS, Tomoda T, Fang Y, Hatten ME (2000) Discoidin domain receptor 1 functions in axon extension of cerebellar granule neurons. Genes Dev 14:2216–2228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Hou G, Vogel W, Bendeck MP (2001) The discoidin domain receptor tyrosine kinase DDR1 in arterial wound repair. J Clin Invest 107:727–735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Vogel WF, Aszodi A, Alves F, Pawson T (2001) Discoidin domain receptor 1 tyrosine kinase has an essential role in mammary gland development. Mol Cell Biol 21:2906–2917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Perez JL, Jing SQ, Wong TW (1996) Identification of two isoforms of the Cak receptor kinase that are coexpressed in breast tumor cell lines. Oncogene 12:1469–1477

    CAS  PubMed  Google Scholar 

  110. Weiner HL, Huang H, Zagzag D, Boyce H, Lichtenbaum R, Ziff EB (2000) Consistent and selective expression of the discoidin domain receptor-1 tyrosine kinase in human brain tumors. Neurosurgery 47:1400–1409

    Article  CAS  PubMed  Google Scholar 

  111. Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y et al (2007) Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131:1190–1203

    Article  CAS  PubMed  Google Scholar 

  112. Alves F, Vogel W, Mossie K, Millauer B, Hofler H, Ullrich A (1995) Distinct structural characteristics of discoidin I subfamily receptor tyrosine kinases and complementary expression in human cancer. Oncogene 10:609–618

    CAS  PubMed  Google Scholar 

  113. Barker KT, Martindale JE, Mitchell PJ, Kamalati T, Page MJ, Phippard DJ, Dale TC, Gusterson BA, Crompton MR (1995) Expression patterns of the novel receptor-like tyrosine kinase DDR, in human breast tumours. Oncogene 10:569–575

    CAS  PubMed  Google Scholar 

  114. Yang SH, Baek HA, Lee HJ, Park HS, Jang KY, Kang MJ, Lee DG, Lee YC, Moon WS, Chung MJ (2010) Discoidin domain receptor 1 is associated with poor prognosis of non-small cell lung carcinomas. Oncol Rep 24:311–319

    CAS  PubMed  Google Scholar 

  115. Ram R, Lorente G, Nikolich K, Urfer R, Foehr E, Nagavarapu U (2006) Discoidin domain receptor-1a (DDR1a) promotes glioma cell invasion and adhesion in association with matrix metalloproteinase-2. J Neurooncol 76:239–248

    Article  CAS  PubMed  Google Scholar 

  116. Balkwill FR, Capasso M, Hagemann T (2012) The tumor microenvironment at a glance. J Cell Sci 125:5591–5596

    Article  CAS  PubMed  Google Scholar 

  117. Kamohara H, Yamashiro S, Galligan C, Yoshimura T (2001) Discoidin domain receptor 1 isoform-a (DDR1alpha) promotes migration of leukocytes in three-dimensional collagen lattices. FASEB J 15:2724–2726

    CAS  PubMed  Google Scholar 

  118. Miao L, Zhu S, Wang Y, Li Y, Ding J, Dai J, Cai H, Zhang D, Song Y (2013) Discoidin domain receptor 1 is associated with poor prognosis of non-small cell lung cancer and promotes cell invasion via epithelial-to-mesenchymal transition. Med Oncol 30:626

    Article  PubMed  CAS  Google Scholar 

  119. Ruiz PA, Jarai G (2011) Collagen I induces discoidin domain receptor (DDR) 1 expression through DDR2 and a JAK2-ERK1/2-mediated mechanism in primary human lung fibroblasts. J Biol Chem 286:12912–12923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Shintani Y, Fukumoto Y, Chaika N, Svoboda R, Wheelock MJ, Johnson KR (2008) Collagen I-mediated up-regulation of N-cadherin requires cooperative signals from integrins and discoidin domain receptor 1. J Cell Biol 180:1277–1289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Suh HN, Han HJ (2011) Collagen I regulates the self-renewal of mouse embryonic stem cells through alpha2beta1 integrin- and DDR1-dependent Bmi-1. J Cell Physiol 226:3422–3432

    Article  CAS  PubMed  Google Scholar 

  122. Xu H, Bihan D, Chang F, Huang PH, Farndale RW, Leitinger B (2012) Discoidin domain receptors promote alpha1beta1- and alpha2beta1-integrin mediated cell adhesion to collagen by enhancing integrin activation. PLoS One 7, e52209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Yeh YC, Lin HH, Tang MJ (2012) A tale of two collagen receptors, integrin β1 and discoidin domain receptor 1, in epithelial cell differentiation. Am J Physiol Cell Physiol 303:C1207–C1217

    Article  CAS  PubMed  Google Scholar 

  124. Roarty K, Serra R (2007) Wnt5a is required for proper mammary gland development and TGF-beta-mediated inhibition of ductal growth. Development 134:3929–3939

    Article  CAS  PubMed  Google Scholar 

  125. Iwai LK, Chang F, Huang PH (2013) Phosphoproteomic analysis identifies insulin enhancement of discoidin domain receptor 2 phosphorylation. Cell Adhes Migr 7:161–164

    Article  Google Scholar 

  126. Kim HG, Hwang SY, Aaronson SA, Mandinova A, Lee SW (2011) DDR1 receptor tyrosine kinase promotes prosurvival pathway through Notch1 activation. J Biol Chem 286:17672–17681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Zhang S, Bu X, Zhao H, Yu J, Wang Y, Li D, Zhu C, Zhu T, Ren T, Liu X, Yao L, Su J (2014) A host deficiency of discoidin domain receptor 2 (DDR2) inhibits both tumor angiogenesis and metastasis. J Pathol 232:436–448

    Article  CAS  PubMed  Google Scholar 

  128. Ren T, Zhang J, Liu X, Yao L (2013) Increased expression of discoidin domain receptor 2 (DDR2): a novel independent prognostic marker of worse outcome in breast cancer patients. Med Oncol 30:397

    Article  PubMed  CAS  Google Scholar 

  129. Fu HL, Sohail A, Valiathan RR, Wasinski BD, Kumarasiri M, Mahasenan KV, Bernardo MM, Tokmina-Roszyk D, Fields GB, Mobashery S, Fridman R (2013) Shedding of discoidin domain receptor 1 by membrane-type matrix metalloproteinases. J Biol Chem 288:12114–12129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Area de Biologia Tumoral, Departamento de Bioquímica Clínica, Facultad de Quimica, Universidad de la República, Av. Gral. Flores 2124, Montevideo, Uruguay

    Marta Marco Ph.D.

  2. Laboratorio de Biotecnología, Polo Tecnológico de Pando, Facultad de Química, Universidad de la República, Montevideo, Uruguay

    Marta Marco Ph.D.

  3. Unidad de Microbiología Molecular, Instituto de Investigaciones Biológicas Clemente Estable, IIBCE, Av. Italia 3318, Montevideo, Uruguay

    Paul R. Gill Ph.D.

  4. El Grupo Esmeralda Uruguay, Sierras de Rocha, IIBCE, Av. Italia 3318, Montevideo, Uruguay

    Paul R. Gill Ph.D.

Authors
  1. Marta Marco Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul R. Gill Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marta Marco Ph.D. .

Editor information

Editors and Affiliations

  1. Department of Pathology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA

    Rafael Fridman

  2. Division of Cancer Biology, The Institute of Cancer Research, London, United Kingdom

    Paul H. Huang

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this chapter

Cite this chapter

Marco, M., Gill, P.R. (2016). DDRs in Healthy and Cancerous Reproductive Systems. In: Fridman, R., Huang, P. (eds) Discoidin Domain Receptors in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-6383-6_9

Download citation

Publish with us

Policies and ethics

Search

Navigation