Skip to main content

Role of Microenvironment in Regulating Stem Cell and Tumor Initiating Cancer Cell Behavior and Its Potential Therapeutic Implications

  • Chapter
  • First Online:
Stem Cells and Cancer Stem Cells, Volume 11

Part of the book series: Stem Cells and Cancer Stem Cells ((STEM,volume 11))

  • 1266 Accesses

Abstract

Microenvironment plays a key role in controlling stem cell fate and thereby regulating tissue homeostasis and repair. It consists of acellular and cellular components that interact with stem cells and their progenitors and through signaling cascades influence balance between self-renewal, differentiation and dormancy. Under pathological conditions, disruptions in microenvironment can generate signals that stimulate untimely or aberrant stem cell differentiation or self-renewal, or activate de-differentiation of progenitor cells, leading to diseased states such as cancer. However, while unaltered microenvironment can restrain transformed cell behavior inhibiting malignant phenotypes, transformed cancer cells that exhibit resistance to conventional therapies and tumor initiating capacity are capable of inducing more permissive and immunotolerant microenvironment that promotes tumor growth and metastasis. Better understanding of their behavior and interactions with microenvironment opens up novel avenues for devising more efficacious cancer therapies.

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

Access this chapter

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

  • Aboussekhra A (2011) Role of cancer-associated fibroblasts in breast cancer development and prognosis. Int J Dev Biol 55:841–849

    Article  PubMed  Google Scholar 

  • Ansieau S, Bastid J, Doreau A, Morel AP, Bouchet BP, Thomas C, Fauvet F, Puisieux I, Doglioni C, Piccinin S, Maestro R, Voeltzel T, Selmi A, Valsesia-Wittmann S, Caron de Fromentel C, Puisieux A (2008) Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence. Cancer Cell 14:79–89

    Article  PubMed  CAS  Google Scholar 

  • Barclay AN, Brown MH (2006) The SIRP family of receptors and immune regulation. Nat Rev Immunol 6:457–464

    Article  PubMed  CAS  Google Scholar 

  • Boehnke K, Mirancea N, Pavesio A, Fusenig NE, Boukamp P, Stark HJ (2007) Effects of fibroblasts and microenvironment on epidermal regeneration and tissue function in long-term skin equivalents. Eur J Cell Biol 86:731–746

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Celia-Terrassa T, Meca-Cortes O, Mateo F, de Paz AM, Rubio N, Arnal-Estape A, Ell BJ, Bermudo R, Diaz A, Guerra-Rebollo M, Lozano JJ, Estaras C, Ulloa C, Alvarez-Simon D, Mila J, Vilella R, Paciucci R, Martinez-Balbas M, de Herreros AG, Gomis RR, Kang Y, Blanco J, Fernandez PL, Thomson TM (2012) Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells. J Clin Invest 122:1849–1868

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Li Y, Yu TS, McKay RM, Burns DK, Kernie SG, Parada LF (2012) A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 488:522–526

    Article  PubMed  CAS  Google Scholar 

  • Coppe JP, Desprez PY, Krtolica A, Campisi J (2010) The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol 5:99–118

    Article  PubMed  CAS  Google Scholar 

  • Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942–949

    Article  PubMed  CAS  Google Scholar 

  • de Visser KE, Korets LV, Coussens LM (2005) De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell 7:411–423

    Article  PubMed  Google Scholar 

  • Di Tomaso T, Mazzoleni S, Wang E, Sovena G, Clavenna D, Franzin A, Mortini P, Ferrone S, Doglioni C, Marincola FM, Galli R, Parmiani G, Maccalli C (2010) Immunobiological characterization of cancer stem cells isolated from glioblastoma patients. Clin Cancer Res 16:800–813

    Article  PubMed  Google Scholar 

  • Driessens G, Beck B, Caauwe A, Simons BD, Blanpain C (2012) Defining the mode of tumour growth by clonal analysis. Nature 488:527–530

    Article  PubMed  CAS  Google Scholar 

  • Eliasson P, Jonsson JI (2010) The hematopoietic stem cell niche: low in oxygen but a nice place to be. J Cell Physiol 222:17–22

    Article  PubMed  CAS  Google Scholar 

  • Hermitte F, Brunet de la Grange P, Belloc F, Praloran V, Ivanovic Z (2006) Very low O2 concentration (0.1%) favors G0 return of dividing CD34+ cells. Stem Cells 24:65–73

    Article  PubMed  Google Scholar 

  • Ilic D, Giritharan G, Zdravkovic T, Caceres E, Genbacev O, Fisher SJ, Krtolica A (2009) Derivation of human embryonic stem cell lines from biopsied blastomeres on human feeders with minimal exposure to xenomaterials. Stem Cells Dev 18:1343–1350

    Article  PubMed  CAS  Google Scholar 

  • Inomata K, Aoto T, Binh NT, Okamoto N, Tanimura S, Wakayama T, Iseki S, Hara E, Masunaga T, Shimizu H, Nishimura EK (2009) Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation. Cell 137:1088–1099

    Article  PubMed  CAS  Google Scholar 

  • Jang YY, Sharkis SJ (2007) A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche. Blood 110:3056–3063

    Article  PubMed  CAS  Google Scholar 

  • Korkaya H, Kim GI, Davis A, Malik F, Henry NL, Ithimakin S, Quraishi AA, Tawakkol N, D’Angelo R, Paulson AK, Chung S, Luther T, Paholak HJ, Liu S, Hassan KA, Zen Q, Clouthier SG, Wicha MS (2012) Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER2+ breast cancer by expanding the cancer stem cell population. Mol Cell 47:570–584

    Article  PubMed  CAS  Google Scholar 

  • Krtolica A, Larocque N, Genbacev O, Ilic D, Coppe JP, Patil CK, Zdravkovic T, McMaster M, Campisi J, Fisher SJ (2011) GROalpha regulates human embryonic stem cell self-renewal or adoption of a neuronal fate. Differentiation 81:222–232

    Article  PubMed  CAS  Google Scholar 

  • Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF, Hilsenbeck SG, Pavlick A, Zhang X, Chamness GC, Wong H, Rosen J, Chang JC (2008) Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst 100:672–679

    Article  PubMed  CAS  Google Scholar 

  • Li HJ, Reinhardt F, Herschman HR, Weinberg RA (2012) Cancer-stimulated mesenchymal stem cells create a carcinoma stem cell niche via prostaglandin E2 signaling. Cancer Discov 2:840–855

    Article  PubMed  CAS  Google Scholar 

  • Parrinello S, Samper E, Krtolica A, Goldstein J, Melov S, Campisi J (2003) Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat Cell Biol 5:741–747

    Article  PubMed  CAS  Google Scholar 

  • Piccirillo SG, Reynolds BA, Zanetti N, Lamorte G, Binda E, Broggi G, Brem H, Olivi A, Dimeco F, Vescovi AL (2006) Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 444:761–765

    Article  PubMed  CAS  Google Scholar 

  • Pistollato F, Chen HL, Schwartz PH, Basso G, Panchision DM (2007) Oxygen tension controls the expansion of human CNS precursors and the generation of astrocytes and oligodendrocytes. Mol Cell Neurosci 35:424–435

    Article  PubMed  CAS  Google Scholar 

  • Reiman JM, Knutson KL, Radisky DC (2010) Immune promotion of epithelial-mesenchymal transition and generation of breast cancer stem cells. Cancer Res 70:3005–3008

    Article  PubMed  Google Scholar 

  • Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–111

    Article  PubMed  CAS  Google Scholar 

  • Russell RC, Fang C, Guan KL (2011) An emerging role for TOR signaling in mammalian tissue and stem cell physiology. Development 138:3343–3356

    Article  PubMed  CAS  Google Scholar 

  • Rygiel TP, Karnam G, Goverse G, van der Marel AP, Greuter MJ, van Schaarenburg RA, Visser WF, Brenkman AB, Molenaar R, Hoek RM, Mebius RE, Meyaard L (2012) CD200-CD200R signaling suppresses anti-tumor responses independently of CD200 expression on the tumor. Oncogene 31:2979–2988

    Article  PubMed  CAS  Google Scholar 

  • Santisteban M, Reiman JM, Asiedu MK, Behrens MD, Nassar A, Kalli KR, Haluska P, Ingle JN, Hartmann LC, Manjili MH, Radisky DC, Ferrone S, Knutson KL (2009) Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells. Cancer Res 69:2887–2895

    Article  PubMed  CAS  Google Scholar 

  • Scaffidi P, Misteli T (2008) Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing. Nat Cell Biol 10:452–459

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Schepers AG, Snippert HJ, Stange DE, van den Born M, van Es JH, van de Wetering M, Clevers H (2012) Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science 337:730–735

    Article  PubMed  CAS  Google Scholar 

  • Shipitsin M, Campbell LL, Argani P, Weremowicz S, Bloushtain-Qimron N, Yao J, Nikolskaya T, Serebryiskaya T, Beroukhim R, Hu M, Halushka MK, Sukumar S, Parker LM, Anderson KS, Harris LN, Garber JE, Richardson AL, Schnitt SJ, Nikolsky Y, Gelman RS, Polyak K (2007) Molecular definition of breast tumor heterogeneity. Cancer Cell 11:259–273

    Article  PubMed  CAS  Google Scholar 

  • Weaver VM, Petersen OW, Wang F, Larabell CA, Briand P, Damsky C, Bissell MJ (1997) Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies. J Cell Biol 137:231–245

    Article  PubMed  CAS  Google Scholar 

  • Wu A, Wiesner S, Xiao J, Ericson K, Chen W, Hall WA, Low WC, Ohlfest JR (2007) Expression of MHC I and NK ligands on human CD133+ glioma cells: possible targets of immunotherapy. J Neurooncol 83:121–131

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ana Krtolica .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Krtolica, A. (2014). Role of Microenvironment in Regulating Stem Cell and Tumor Initiating Cancer Cell Behavior and Its Potential Therapeutic Implications. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 11. Stem Cells and Cancer Stem Cells, vol 11. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7329-5_14

Download citation

Publish with us

Policies and ethics