Skip to main content
SpringerLink
Log in

Bone Marrow Derived Mesenchymal Stem/Stromal Cells and Tumor Growth

  • Chapter
  • First Online:
The Tumor Microenvironment

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

  • 2824 Accesses

Abstract

Carcinoma associated fibroblasts (CAFs) play an important role in the growth of epithelial solid tumors. The origin of these tumor or CAFs has not been conclusively established. There is experimental evidence to suggest that part of the tumor or CAFs may arise from bone marrow derived mesenchymal stromal/stem cells or MSCs. It is well known that bone marrow derived MSCs can give rise to cells of different lineages: muscle, bone, fat, and cartilage. Based on recent work from our own laboratory and that of others, we now suggest that human BM-derived MSCs exposed to tumor-conditioned medium (TCM) over a prolonged period of time can give rise to cells that assume a CAF-like phenotype. Thus, MSCs may be a source of CAFs and can be used experimentally for modeling tumor-stroma interactions. Although the importance of the dialog between cancer cells and other components of the tumor milieu has been increasingly appreciated, it is as yet unclear whether the stromal cells themselves harbor cancer promoting mutations or changes. Activated stromal cells have been shown to promote tumor growth and metastasis in experimental models and we speculate on the possibility of increased activation of bone marrow derived MSCs by higher levels of chemokines under certain physiological situations and how this may impact tumor growth.

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 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

  • Albain KS, Unger JM, Crowley JJ, Coltman CA Jr, Hershman DL (2009) Racial disparities in cancer survival among randomized clinical trials patients of the Southwest Oncology Group. J Natl Cancer Inst 101(14):984–992

    Article  PubMed  Google Scholar 

  • Alexe G, Dalgin GS, Scanfeld D et al (2007) High expression of lymphocyte-associated genes in node-negative HER2+ breast cancers correlates with lower recurrence rates. Can Research 67:10669–10676

    Article  CAS  Google Scholar 

  • Allinen M, Beroukhim R et al (2004) Molecular characterization of the tumor microenvironment in breast cancer. Cancer Cell 6(1):17–32

    Article  PubMed  CAS  Google Scholar 

  • Amend K, Hicks D, Ambrosone, CB (2006) Breast cancer in African-American women: differences in tumor biology from European American women. Cancer Res 66:8327–8330

    Article  PubMed  CAS  Google Scholar 

  • Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–545

    Article  PubMed  CAS  Google Scholar 

  • Bissell MJ, Radisky D. (2001) Putting tumors in context. Nature Rev Cancer 1:46–54

    Article  CAS  Google Scholar 

  • Campbell I, Polyak K, Haviv I (2009) Clonal mutations in the cancer associated fibroblasts: the case against genetic coevolution. Cancer Res 69:6765–6769

    Article  PubMed  CAS  Google Scholar 

  • Chaffer CL, Brennan JP, Slavin JL et al (2006) Mesenchymal-to-epithelial transition facilitates bladder cancer metastasis: role of fibroblast growth factor receptor-2. Cancer Res 66:11271–11278

    Article  PubMed  CAS  Google Scholar 

  • Chang HY, Nuyten DS, Sneddon JB et al (2005) Robustness scalability and integration of a wound response gene expression signature in predicting breast cancer survival. Proc Natl Acad Sci U S A 102(10): 3738–3743

    Article  PubMed  CAS  Google Scholar 

  • Direkze NC, Hodivala-Dilke K, Jeffery R et al (2004) Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts. Cancer Res 64:8492–8495

    Article  PubMed  CAS  Google Scholar 

  • Dudley AC, Shih SC, Cliffe AR et al (2008) Attenuated p53 activation in tumor-associated stromal cells accompanies decreased sensitivity to etoposide and vincristine. Br J Cancer 99:118–125

    Article  PubMed  CAS  Google Scholar 

  • Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315:1650–1659

    Article  PubMed  CAS  Google Scholar 

  • Eng C, Leone G, Orloff MS, Ostrowski MC (2009) Genomic alterations in tumor stroma. Cancer Res 69:6759–6764

    Article  PubMed  CAS  Google Scholar 

  • Finak G, Bertos N, Pepin F et al (2008) Stromal gene expression predicts clinical outcome in breast cancer. Nat Med 14:518–527

    Article  PubMed  CAS  Google Scholar 

  • Fox J M, Chamberlain G, Ashton BA, Middleton J (2007) Recent advances into the understanding of mesenchymal stem cell trafficking. Br J Haematol 137:491–502

    Article  PubMed  CAS  Google Scholar 

  • Fukuma N, Akimitsu N, Hamamoto H, Kusuhara H, Sugiyama Y, Sekimizu K (2003) A role of the Duffy antigen for the maintenance of plasma chemokine concentrations. Biochem Biophys Res Commun 303:137–139

    Article  PubMed  CAS  Google Scholar 

  • Guo X, Oshima H, Kitmura T et al (2008) Stromal fibroblasts activated by tumor cells promote angiogenesis in mouse gastric cancer. J Biol Chem 283:19864–19871

    Article  PubMed  CAS  Google Scholar 

  • Hawsawi NM, Ghebeh H, Hendrayani SF et al (2008) Breast carcinoma-associated fibroblasts and their counterparts display neoplastic-specific changes. Cancer Res 68:2717–2725

    Article  PubMed  CAS  Google Scholar 

  • Hu M, Polyak K (2008) Molecular characterisation of the tumour microenvironment in breast cancer. Eur J Cancer 44(18):2760–2765

    Article  PubMed  CAS  Google Scholar 

  • Hung SC, Deng WP, Yang WK et al (2005) Mesenchymal stem cell targeting of microscopic tumors and tumor stroma development monitored by noninvasive in vivo positron emission tomography imaging. Clin Cancer Res 11:7749–7756

    Article  PubMed  CAS  Google Scholar 

  • Iwamoto S, Mihara K, Dowining JR, Pui C-H, Campana D (2007) Mesenchymal cells regulate the response of acute lymphoblastic leukemia to asparaginase. J Clin Invest 117:1049–1057

    Article  PubMed  CAS  Google Scholar 

  • Jodele S, Chantrain CF, Blavier L, Lutzko C, Crooks GM et al (2005) The contribution of bone marrow-derived cells to the tumor vasculature in neuroblastoma is matrix metalloproteinase-9 dependent. Cancer Res 65:3200–3208

    PubMed  CAS  Google Scholar 

  • Karnoub AE, Dash AB, Vo AP et al (2007) Mesenchymal stem cells within tumor stroma promote breast cancer metastasis. Nature 449:557–563

    Article  PubMed  CAS  Google Scholar 

  • Koukourakis MI, Giatromanolaki A, Harris AL et al (2006) Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: a metabolic survival role for tumor-associated stroma. Cancer Res 66:632–637

    Article  PubMed  CAS  Google Scholar 

  • Koyama H, Kobayashi N, Harada M, Takeoka M, Kawai Y et al (2008) Significance of tumor-associated stroma in promotion of intratumoral lymphangiogenesis: pivotal role of a hyaluronan-rich tumor microenvironment. Am J Pathol 172:179–193

    Article  PubMed  CAS  Google Scholar 

  • Kroemer G, Pouyssegur J (2008) Tumor cell metabolism: cancer’s Achilles’ heel. Cancer Cell 13:472–482

    Article  PubMed  CAS  Google Scholar 

  • Lee JS, Frevert CW, Wurfel MM et al (2003) Duffy antigen facilitates movement of chemokine across the endothelium in vitro and promotes neutrophil transmigration in vitro and in vivo. J Immunol 170(10):5244–5251

    PubMed  CAS  Google Scholar 

  • Lentsch AB (2002) The Duffy antigen/receptor for chemokines (DARC) and prostate cancer. A role as clear as black and white? The FASEB Journal 16:1093–1095

    Article  CAS  Google Scholar 

  • Liu XH, Hadley TJ, Xu L, Peiper SC, Ray PE (1999) Up-regulation of Duffy antigen receptor expression in children with renal disease. Kidney Int 55(4):1491–1500

    Article  PubMed  CAS  Google Scholar 

  • Mantovani A, Schioppa T, Porta C, Allavena P, Sica A (2006) Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Rev 25:315–322

    Article  PubMed  Google Scholar 

  • Martin DN, Boersma BJ et al (2009). Differences in the tumor microenvironment between African-American and European-American breast cancer patients. PloS One 4:1–14

    Article  Google Scholar 

  • Mayr FB, Spiel AO, Leitner JM, Firbas C, Kliegel T, Jilma B (2007) Ethnic differences in plasma levels of interleukin-8 (IL-8) and granulocyte colony stimulating factor (G-CSF). Transl Res 149(1):10–14

    Article  PubMed  CAS  Google Scholar 

  • Mishra PJ, Mishra PJ, Humeniuk R et al (2008) Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. Cancer Res 68:4331–4339

    Article  PubMed  CAS  Google Scholar 

  • Nakamizo A, Marini F, Amano T et al (2005) Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Res 65:3307–3318

    PubMed  CAS  Google Scholar 

  • Ogawa M, LaRue AC, Drake CJ (2006) Hematopoietic origin of fibroblasts/myofibroblasts: its pathophysiologic implications. Blood 108:2893–2896

    Article  PubMed  CAS  Google Scholar 

  • Orimo A, Gupta PB, Sgroi DC et al (2005) Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121:335–348

    Article  PubMed  CAS  Google Scholar 

  • Patocs A, Zhang L, Xu Y et al (2007) Breast-cancer stromal cells with TP53 mutations and nodal metastases. N Engl J Med 357:2543–2551

    Article  PubMed  CAS  Google Scholar 

  • Picinich SC, Mishra PJ, Mishra PJ, Glod J, Banerjee D (2007) The therapeutic potential of mesenchymal stem cells. Expert Opin Biol Ther 7:965–973

    Article  PubMed  CAS  Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  PubMed  CAS  Google Scholar 

  • Pruenster M, Mudde L, Bombosi P et al (2009) The Duffy antigen receptor for chemokines transports chemokines and supports their promigratory activity. Nat Immunol 10:101–108

    Article  PubMed  CAS  Google Scholar 

  • Radisky DC (2005) Epithelial-mesenchymal transition. J Cell Sci 118:4325–4326

    Article  PubMed  CAS  Google Scholar 

  • Ries L, Eisner M, Kosary M (2002) SEER Cancer Statistics Review, 1973–1999. National Cancer Institute, Bethesda, MD

    Google Scholar 

  • Salomon AV, Thiery JP. (2003) Host microenvironment in breast cancer development Epithelial–mesenchymal transition in breast cancer development. Breast Cancer Res 5:101–106

    Article  Google Scholar 

  • Samudio I, Fiegl M, McQueen T et al (2008) The Warburg effect in leukemia-stroma cocultures is mediated by mitochondrial uncoupling associated with uncoupling protein-2 activation. Cancer Res 68:5198–5205

    Article  PubMed  CAS  Google Scholar 

  • Shen H, Schuster R, Stringer KF, Waltz SE, Lentsch AB (2006) The Duffy antigen/receptor for chemokines (DARC) regulates prostate tumor growth. FASEB J 20:59–64

    Article  PubMed  CAS  Google Scholar 

  • Shinagawa K, Kiatadai Y, Ohara E et al (2009) Mesenchymal stem cells migrate to tumor stroma and enhance tumor growth in an orthotopic nude mouse model of colon cancer. Abstract 3156. p314 Proc of 100th Annual Meeting AACR, Denver,CO, 18–22 April 2009

    Google Scholar 

  • Sorlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98:10869–10874

    Article  PubMed  CAS  Google Scholar 

  • Spaeth EL, Dembinski JL, Kate Sasser A et al (2009) Mesenchymals stem cell transition to tumor associated fibroblasts contributes to fibrovascular network expansion and tumor progression. PloS One 4:1–11

    Article  Google Scholar 

  • Studeny M, Marini FC, Champlin RE et al (2002) Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Res 62:3603–3608

    PubMed  CAS  Google Scholar 

  • Studeny M, Marini FC, Dembinski JL et al (2004) Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents. J Natl Cancer Inst 96:1593–1603

    Article  PubMed  CAS  Google Scholar 

  • Tournamille C, Colin Y, Cartron JP, Le Van Kim C (1995) Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals. Nat Genet 10:224–228

    Article  PubMed  CAS  Google Scholar 

  • Tsujino T, Seshimo I, Yamamoto H, Ngan CY, Ezumi K et al (2007) Stromal myofibroblasts predict disease recurrence for colorectal cancer. Clin Cancer Res 13:2082–2090

    Article  PubMed  CAS  Google Scholar 

  • Udagawa T, Puder M, Wood M, Schaefer BC, D’Amato RJ (2006) Analysis of tumor-associated stromal cells using SCID GFP transgenic mice: contribution of local and bone marrow-derived host cells. FASEB J 20:95–102

    Article  PubMed  CAS  Google Scholar 

  • van de Vijver MJ, He YD, van’t Veer LJ et al (2002) Gene expression profiling predicts clinical outcome of breast cancer. N Engl J Med 347(25):1999–2009

    Article  PubMed  CAS  Google Scholar 

  • Wadhwa M, Seghatchian MJ, Dilger P, Contreras M, Thorpe R (2000) Cytokine accumulation in stored red cell concentrates: effect of buffy-coat removal and leucoreduction. Transfus Sci 23(1):7–16

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Klijn JG, Zhang Y et al (2005) Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 365:671–679

    PubMed  CAS  Google Scholar 

  • Wang J, Ou ZL, Hou YF, Luo JM, Shen ZZ, Ding J, Shao ZM (2006) Enhanced expression of Duffy antigen receptor for chemokines by breast cancer cells attenuates growth and metastasis potential. Oncogene 25:7201–7211

    Article  PubMed  CAS  Google Scholar 

  • Weber F, Xu Y, Zhang L, Patocs A, Shen L, Platzer P, Eng C (2007) Microenvironmental genomic alterations and clinicopathological behavior in head and neck squamous cell carcinoma. JAMA 297:187–195

    Article  PubMed  CAS  Google Scholar 

  • Worthley DL, Ruszkiewicz A, Davies R et al (2009) Human Gastrointestinal neoplasia associated myofibroblasts can develop from bone marrow derived cells following allogeneic stem cell transplantation. Stem Cells 27:1463–1468

    Article  PubMed  CAS  Google Scholar 

  • Yazhou C, Wenlv S, Weidong Z, Licun W (2004) Clinicopathological significance of stromal myofibroblasts in invasive ductal carcinoma of the breast. Tumor Biol 25:290–295

    Article  Google Scholar 

  • Zhang Y, Daquinag A, Traktuev DO et al (2009) White adipose tissue cells are recruited by experimental tumors and promote cancer progression in mouse models. Cancer Res 69:5259–5265

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 195 Little Albany Street, New Brunswick, NJ, 08901, USA

    Debabrata Banerjee

  2. Department of Pharmacology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 195 Little Albany Street, New Brunswick, NJ, 08901, USA

    Debabrata Banerjee

Authors
  1. Pravin J. Mishra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Debabrata Banerjee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Debabrata Banerjee .

Editor information

Editors and Affiliations

  1. Genzyme Corporation, Mountain Rd. 1, Framingham, 01701-9322, Massachusetts, USA

    Rebecca G. Bagley

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Mishra, P.J., Banerjee, D. (2010). Bone Marrow Derived Mesenchymal Stem/Stromal Cells and Tumor Growth. In: Bagley, R. (eds) The Tumor Microenvironment. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6615-5_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-6615-5_13

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4419-6614-8

  • Online ISBN: 978-1-4419-6615-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation