Skip to main content
SpringerLink
Log in

Stem Cell-Secreted Factors in the Tumor Microenvironment

  • Chapter
  • First Online:
Tumor Microenvironment

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1277))

Abstract

The importance of the microenvironment in tumor development and their resistance to drugs is increasingly well known. This microenvironment is composed of different cell types, among which cells with stemness properties such as cancer stem cells (CSCs) and mesenchymal stem cells (MSCs) are distinguished for their relevant role in tumor proliferation, angiogenesis, metastasis, and drug resistance. The relationship between these stem cells (SCs) and tumor microenvironment is conducted by the secretome, consisting of several factors, cytokines, chemokines, and hormones released to the surrounding stroma, which plays a deterministic role in tumor hallmarks. Knowing the intrinsic and complex communication network that SCs establish with the microenvironment will allow to address the tumor processes responsible for cancer progression and the generation of new targeted therapeutic approaches useful in the clinic arena.

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. Caiado F, Silva-Santos B, Norell H (2016) Intra-tumour heterogeneity – going beyond genetics. FEBS J 283:2245–2258

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  4. Joyce J, Quail D (2013) Microenvironmental regulation of tumor progression and metastasis. Nat Med 19:1423–1437

    Article  CAS  Google Scholar 

  5. Junttila MR, De Sauvage FJ (2013) Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 501(7467):346–354

    Article  CAS  Google Scholar 

  6. Hui L, Chen Y (2015) Tumor microenvironment: sanctuary of the devil. Cancer Lett 368(1):7–13

    Article  CAS  Google Scholar 

  7. Yeldag G, Rice A, del Rio Hernández A (2018) Chemoresistance and the self-maintaining tumor microenvironment. Cancers (Basel) 10(12):pii: E471

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Qian C-N, Tan M-H, Yang J-P, Cao Y (2016) Revisiting tumor angiogenesis: vessel co-option, vessel remodeling, and cancer cell-derived vasculature formation. Chin J Cancer 35:10

    Article  CAS  Google Scholar 

  10. Carmeliet P, Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473:298–307

    Article  CAS  Google Scholar 

  11. Weis SM, Cheresh DA (2011) Tumor angiogenesis: molecular pathways and therapeutic targets. Nat Med 17:1359–1370

    Article  CAS  Google Scholar 

  12. Turley SJ, Cremasco V, Astarita JL (2015) Immunological hallmarks of stromal cells in the tumour microenvironment. Nat Rev Immunol 15:669–682

    Article  CAS  Google Scholar 

  13. Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR (1999) Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res 59(19):5002–5011

    CAS  Google Scholar 

  14. Orimo A, Gupta PB, Sgroi DC, Arenzana-Seisdedos F, Delaunay T, Naeem R 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  CAS  Google Scholar 

  15. Hwang RF, Moore T, Arumugam T, Ramachandran V, Amos KD, Rivera A et al (2008) Cancer-associated stromal fibroblasts promote pancreatic tumor progression. Cancer Res 68(3):918–926

    Article  CAS  Google Scholar 

  16. Crawford Y, Kasman I, Yu L, Zhong C, Wu X, Modrusan Z et al (2009) PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment. Cancer Cell 15:21–34

    Article  CAS  Google Scholar 

  17. Straussman R, Morikawa T, Shee K, Barzily-Rokni M, Qian ZR, Du J et al (2012) Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature 487:500–504

    Article  CAS  Google Scholar 

  18. Paraiso KHT, Smalley KSM (2013) Fibroblast-mediated drug resistance in cancer. Biochem Pharmacol 85:1033–1041

    Article  CAS  Google Scholar 

  19. Räsänen K, Vaheri A (2010) Activation of fibroblasts in cancer stroma. Exp Cell Res 316:2713–2722

    Article  CAS  Google Scholar 

  20. Vong S, Kalluri R (2011) The role of stromal myofibroblast and extracellular matrix in tumor angiogenesis. Genes Cancer 2:1139–1145

    Article  CAS  Google Scholar 

  21. Zamarron BF, Chen W (2011) Dual roles of immune cells and their factors in cancer development and progression. Int J Biol Sci 7:651–658

    Article  CAS  Google Scholar 

  22. Eyileten C, Majchrzak K, Pilch Z, Tonecka K, Mucha J, Taciak B et al (2016) Immune cells in cancer therapy and drug delivery. Mediat Inflamm 2016:1–13

    Article  CAS  Google Scholar 

  23. Condeelis J, Pollard JW (2006) Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 124:263–266

    Article  CAS  Google Scholar 

  24. Bhowmick NA, Chytil A, Plieth D, Gorska AE, Dumont N, Shappell S et al (2004) TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science 303:848–851

    Article  CAS  Google Scholar 

  25. Lu P, Weaver VM, Werb Z (2012) The extracellular matrix: a dynamic niche in cancer progression. J Cell Biol 196:395–406

    Article  CAS  Google Scholar 

  26. Pickup MW, Mouw JK, Weaver VM (2014) The extracellular matrix modulates the hallmarks of cancer. EMBO Rep 15:1243–1253

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  28. Hernández-Camarero P, Jiménez G, López-Ruiz E, Barungi S, Marchal JA, Perán M (2018) Revisiting the dynamic cancer stem cell model: importance of tumour edges. Crit Rev Oncol Hematol 131:35–45

    Article  Google Scholar 

  29. Ni C, Huang J (2013) Dynamic regulation of cancer stem cells and clinical challenges. Clin Transl Oncol 15:253–258

    Article  Google Scholar 

  30. Visvader JE, Lindeman GJ (2012) Cancer stem cells: current status and evolving complexities. Cell Stem Cell 10:717–728

    Article  CAS  Google Scholar 

  31. Jang J-W, Song Y, Kim S-H, Kim J, Seo HR (2017) Potential mechanisms of CD133 in cancer stem cells. Life Sci 184:25–29

    Article  CAS  Google Scholar 

  32. Charafe-Jauffret E, Ginestier C, Birnbaum D (2009) Breast cancer stem cells: tools and models to rely on. BMC Cancer 9:202

    Article  CAS  Google Scholar 

  33. Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U et al (2004) A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci U S A 101:14228–14233

    Article  CAS  Google Scholar 

  34. Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M et al (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1:313–323

    Article  CAS  Google Scholar 

  35. Malanchi I, Santamaria-Martínez A, Susanto E, Peng H, Lehr H-A, Delaloye J-F et al (2011) Interactions between cancer stem cells and their niche govern metastatic colonization. Nature 481:85–89

    Article  CAS  Google Scholar 

  36. Dean M (2009) ABC transporters, drug resistance, and cancer stem cells. J Mammary Gland Biol Neoplasia 14:3–9

    Article  Google Scholar 

  37. Eyler CE, Rich JN (2008) Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis. J Clin Oncol 26:2839–2845

    Article  CAS  Google Scholar 

  38. Maugeri-Saccà M, Bartucci M, De Maria R (2012) DNA damage repair pathways in cancer stem cells. Mol Cancer Ther 11:1627–1636

    Article  CAS  Google Scholar 

  39. Moore N, Lyle S (2011) Quiescent, slow-cycling stem cell populations in cancer: a review of the evidence and discussion of significance. J Oncol 2011:pii: 396076

    Article  CAS  Google Scholar 

  40. Wels J, Kaplan RN, Rafii S, Lyden D (2008) Migratory neighbors and distant invaders: tumor-associated niche cells. Genes Dev 22:559–574

    Article  CAS  Google Scholar 

  41. Ye J, Wu D, Wu P, Chen Z, Huang J (2014) The cancer stem cell niche: cross talk between cancer stem cells and their microenvironment. Tumor Biol 35:3945–3951

    Article  CAS  Google Scholar 

  42. Klimczak A, Kozlowska U (2016) Mesenchymal stromal cells and tissue-specific progenitor cells: their role in tissue homeostasis. Stem Cells Int 2016:4285215

    Article  CAS  Google Scholar 

  43. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  CAS  Google Scholar 

  44. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini FC, Krause DS et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317

    Article  CAS  Google Scholar 

  45. Bergfeld SA, DeClerck YA (2010) Bone marrow-derived mesenchymal stem cells and the tumor microenvironment. Cancer Metastasis Rev 29:249–261

    Article  Google Scholar 

  46. Dwyer RM, Potter-Beirne SM, Harrington KA, Lowery AJ, Hennessy E, Murphy JM et al (2007) Monocyte chemotactic protein-1 secreted by primary breast tumors stimulates migration of mesenchymal stem cells. Clin Cancer Res 13:5020–5027

    Article  CAS  Google Scholar 

  47. Senst C, Nazari-Shafti T, Kruger S, Höner Zu Bentrup K, Dupin CL, Chaffin AE et al (2013) Prospective dual role of mesenchymal stem cells in breast tumor microenvironment. Breast Cancer Res Treat 137:69–79

    Article  CAS  Google Scholar 

  48. Ridge SM, Sullivan FJ, Glynn SA (2017) Mesenchymal stem cells: key players in cancer progression. Mol Cancer 16:31

    Article  CAS  Google Scholar 

  49. Djouad F, Plence P, Bony C, Tropel P, Apparailly F, Sany J et al (2003) Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood 102:3837–3844

    Article  CAS  Google Scholar 

  50. Zhu W, Huang L, Li Y, Zhang X, Gu J, Yan Y et al (2012) Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. Cancer Lett 315:28–37

    Article  CAS  Google Scholar 

  51. Spaeth EL, Dembinski JL, Sasser AK, Watson K, Klopp A, Hall B et al (2009) Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression. PLoS One 4(4):e4992

    Article  CAS  Google Scholar 

  52. Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW et al (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449:557–563

    Article  CAS  Google Scholar 

  53. Nabha SM, dos Santos EB, Yamamoto HA, Belizi A, Dong Z, Meng H et al (2008) Bone marrow stromal cells enhance prostate cancer cell invasion through type I collagen in an MMP-12 dependent manner. Int J Cancer 122:2482–2490

    Article  CAS  Google Scholar 

  54. Martin FT, Dwyer RM, Kelly J, Khan S, Murphy JM, Curran C et al (2010) Potential role of mesenchymal stem cells (MSCs) in the breast tumour microenvironment: stimulation of epithelial to mesenchymal transition (EMT). Breast Cancer Res Treat 124:317–326

    Article  CAS  Google Scholar 

  55. Suzuki K, Sun R, Origuchi M, Kanehira M, Takahata T, Itoh J et al (2011) Mesenchymal stromal cells promote tumor growth through the enhancement of neovascularization. Mol Med 17:579–587

    Article  CAS  Google Scholar 

  56. Zhang T, Lee Y, Rui Y, Cheng T, Jiang X, Li G (2013) Bone marrow-derived mesenchymal stem cells promote growth and angiogenesis of breast and prostate tumors. Stem Cell Res Ther 4:70

    Article  CAS  Google Scholar 

  57. Mishra PJ, Mishra PJ, Humeniuk R, Medina DJ, Alexe G, Mesirov JP et al (2008) Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. Cancer Res 68:4331–4339

    Article  CAS  Google Scholar 

  58. Hossain A, Gumin J, Gao F, Figueroa J, Shinojima N, Takezaki T et al (2015) Mesenchymal stem cells isolated from human gliomas increase proliferation and maintain stemness of glioma stem cells through the IL-6/gp130/STAT3 pathway. Stem Cells 33:2400–2415

    Article  CAS  Google Scholar 

  59. Jiménez G, Hackenberg M, Catalina P, Boulaiz H, Griñán-Lisón C, García MÁ et al (2018) Mesenchymal stem cell’s secretome promotes selective enrichment of cancer stem-like cells with specific cytogenetic profile. Cancer Lett 429:78–88

    Article  CAS  Google Scholar 

  60. Kuhn NZ, Tuan RS (2010) Regulation of stemness and stem cell niche of mesenchymal stem cells: implications in tumorigenesis and metastasis. J Cell Physiol 222:268–277

    Article  CAS  Google Scholar 

  61. Bissell MJ, Hines WC (2011) Why don’t we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat Med 17:320–329

    Article  CAS  Google Scholar 

  62. Quail DF, Joyce JA (2013) Microenvironmental regulation of tumor progression and metastasis. Nat Med 19:1423–1437

    Article  CAS  Google Scholar 

  63. Paltridge JL, Belle L, Khew-Goodall Y (1834) The secretome in cancer progression. Biochim Biophys Acta 2013:2233–2241

    Google Scholar 

  64. Melzer C, von der Ohe J, Lehnert H, Ungefroren H, Hass R (2017) Cancer stem cell niche models and contribution by mesenchymal stroma/stem cells. Mol Cancer 16:28

    Article  CAS  Google Scholar 

  65. Beck B, Driessens G, Goossens S, Youssef KK, Kuchnio A, Caauwe A et al (2011) A vascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumours. Nature 478:399–403

    Article  CAS  Google Scholar 

  66. Beckermann BM, Kallifatidis G, Groth A, Frommhold D, Apel A, Mattern J et al (2008) VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma. Br J Cancer 99:622–631

    Article  CAS  Google Scholar 

  67. Zhang K, Shi B, Chen J, Zhang D, Zhu Y, Zhou C et al (2010) Bone marrow mesenchymal stem cells induce angiogenesis and promote bladder cancer growth in a rabbit model. Urol Int 84:94–99

    Article  Google Scholar 

  68. Xu C, Wu X, Zhu J (2013) VEGF promotes proliferation of human glioblastoma multiforme stem-like cells through VEGF receptor 2. Sci World J 2013:1–8

    Google Scholar 

  69. Mercurio AM (2019) VEGF/neuropilin signaling in cancer stem cells. Int J Mol Sci 20(3):pii: E490

    Article  CAS  Google Scholar 

  70. Huang W-H, Chang M-C, Tsai K-S, Hung M-C, Chen H-L, Hung S-C (2013) Mesenchymal stem cells promote growth and angiogenesis of tumors in mice. Oncogene 32:4343–4354

    Article  CAS  Google Scholar 

  71. Conroy S, Kruyt FAE, Wagemakers M, Bhat KPL, den Dunnen WFA (2018) IL-8 associates with a pro-angiogenic and mesenchymal subtype in glioblastoma. Oncotarget 9:15721–15731

    Article  Google Scholar 

  72. Lequeux A, Noman MZ, Xiao M, Sauvage D, Van Moer K, Viry E et al (2019) Impact of hypoxic tumor microenvironment and tumor cell plasticity on the expression of immune checkpoints. Cancer Lett 458:13–20

    Article  CAS  Google Scholar 

  73. Lavrentieva A, Majore I, Kasper C, Hass R (2010) Effects of hypoxic culture conditions on umbilical cord-derived human mesenchymal stem cells. Cell Commun Signal 8:18

    Article  CAS  Google Scholar 

  74. Li Z, Bao S, Wu Q, Wang H, Eyler C, Sathornsumetee S et al (2009) Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell 15:501–513

    Article  CAS  Google Scholar 

  75. Kitamura T, Qian B-Z, Pollard JW (2015) Immune cell promotion of metastasis. Nat Rev Immunol 15:73–86

    Article  CAS  Google Scholar 

  76. Soeda A, Park M, Lee D, Mintz A, Androutsellis-Theotokis A, McKay RD et al (2009) Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1α. Oncogene 28:3949–3959

    Article  CAS  Google Scholar 

  77. Lee D-H, Oh SC, Giles AJ, Jung J, Gilbert MR, Park DM (2017) Cardiac glycosides suppress the maintenance of stemness and malignancy via inhibiting HIF-1α in human glioma stem cells. Oncotarget 8(25):40233–40245

    Article  Google Scholar 

  78. Jacobsson H, Harrison H, Hughes É, Persson E, Rhost S, Fitzpatrick P et al (2019) Hypoxia-induced secretion stimulates breast cancer stem cell regulatory signalling pathways. Mol Oncol 13(8):1693–1705

    Article  CAS  Google Scholar 

  79. Zeeshan R, Mutahir Z (2017) Cancer metastasis – tricks of the trade. Bosn J Basic Med Sci 17:172–182

    CAS  Google Scholar 

  80. Long H, Xie R, Xiang T, Zhao Z, Lin S, Liang Z et al (2012) Autocrine CCL5 signaling promotes invasion and migration of CD133+ ovarian cancer stem-like cells via NF-κB-mediated MMP-9 upregulation. Stem Cells 30:2309–2319

    Article  CAS  Google Scholar 

  81. Justilien V, Regala RP, Tseng I-C, Walsh MP, Batra J, Radisky ES et al (2012) Matrix metalloproteinase-10 is required for lung cancer stem cell maintenance, tumor initiation and metastatic potential. PLoS One 7:e35040

    Article  CAS  Google Scholar 

  82. Inoue A, Takahashi H, Harada H, Kohno S, Ohue S, Kobayashi K et al (2010) Cancer stem-like cells of glioblastoma characteristically express MMP-13 and display highly invasive activity. Int J Oncol 37:1121–1131

    CAS  Google Scholar 

  83. Mariya T, Hirohashi Y, Torigoe T, Tabuchi Y, Asano T, Saijo H et al (2016) Matrix metalloproteinase-10 regulates stemness of ovarian cancer stem-like cells by activation of canonical Wnt signaling and can be a target of chemotherapy-resistant ovarian cancer. Oncotarget 7:26806–26822

    Article  Google Scholar 

  84. Chaturvedi P, Gilkes DM, Wong CC, Kshitiz, Luo W, Zhang H et al (2013) Hypoxia-inducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis. J Clin Invest 123:189–205

    Article  CAS  Google Scholar 

  85. So KA, Min KJ, Hong JH, Lee J-K (2015) Interleukin-6 expression by interactions between gynecologic cancer cells and human mesenchymal stem cells promotes epithelial-mesenchymal transition. Int J Oncol 47:1451–1459

    Article  CAS  Google Scholar 

  86. Ritter A, Friemel A, Fornoff F, Adjan M, Solbach C, Yuan J et al (2015) Characterization of adipose-derived stem cells from subcutaneous and visceral adipose tissues and their function in breast cancer cells. Oncotarget 6(33):34475–34493

    Article  Google Scholar 

  87. Wu S, Wang Y, Yuan Z, Wang S, Du H, Liu X et al (2018) Human adipose-derived mesenchymal stem cells promote breast cancer MCF7 cell epithelial-mesenchymal transition by cross interacting with the TGF-β/Smad and PI3K/AKT signaling pathways. Mol Med Rep 19:177–186

    Google Scholar 

  88. McAndrews KM, McGrail DJ, Ravikumar N, Dawson MR (2015) Mesenchymal stem cells induce directional migration of invasive breast cancer cells through TGF-β. Sci Rep 5:16941

    Article  CAS  Google Scholar 

  89. Padua D, Zhang XH-F, Wang Q, Nadal C, Gerald WL, Gomis RR et al (2008) TGFβ primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell 133:66–77

    Article  CAS  Google Scholar 

  90. Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C et al (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438:820–827

    Article  CAS  Google Scholar 

  91. Xu D, Xu H, Ren Y, Liu C, Wang X, Zhang H et al (2012) Cancer stem cell-related gene periostin: a novel prognostic marker for breast cancer. PLoS One 7:e46670

    Article  CAS  Google Scholar 

  92. Wang X, Liu J, Wang Z, Huang Y, Liu W, Zhu X et al (2013) Periostin contributes to the acquisition of multipotent stem cell-like properties in human mammary epithelial cells and breast cancer cells. PLoS One 8:e72962

    Article  CAS  Google Scholar 

  93. Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454(7203):436–444

    Article  CAS  Google Scholar 

  94. Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140:883–899

    Article  CAS  Google Scholar 

  95. Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141:52–67

    Article  CAS  Google Scholar 

  96. Mantovani A (2010) Molecular pathways linking inflammation and cancer. Curr Mol Med 10:369–373

    Article  CAS  Google Scholar 

  97. De Miguel MP, Fuentes-Julián S, Blázquez-Martínez A, Pascual CY, Aller MA, Arias J et al (2012) Immunosuppressive properties of mesenchymal stem cells: advances and applications. Curr Mol Med 12:574–591

    Article  Google Scholar 

  98. Liubomirski Y, Lerrer S, Meshel T, Morein D, Rubinstein-Achiasaf L, Sprinzak D et al (2019) Notch-mediated tumor-stroma-inflammation networks promote invasive properties and CXCL8 expression in triple-negative breast cancer. Front Immunol 10:804

    Article  CAS  Google Scholar 

  99. Yoshimura A, Muto G (2011) TGF-β function in immune suppression. Curr Top Microbiol Immunol 350:127–147

    CAS  Google Scholar 

  100. Liu S, Ginestier C, Ou SJ, Clouthier SG, Patel SH, Monville F et al (2011) Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer Res 71:614–624

    Article  CAS  Google Scholar 

  101. Nomura A, Gupta VK, Dauer P, Sharma NS, Dudeja V, Merchant N et al (2018) NFκB-mediated invasiveness in CD133 + pancreatic TICs is regulated by autocrine and paracrine activation of IL1 signaling. Mol Cancer Res 16:162–172

    Article  CAS  Google Scholar 

  102. Chen M-S, Lin C-Y, Chiu Y-H, Chen C-P, Tsai P-J, Wang H-S (2018) IL-1β-induced matrix metalloprotease-1 promotes mesenchymal stem cell migration via PAR1 and G-protein-coupled signaling pathway. Stem Cells Int 2018:3524759

    Google Scholar 

  103. Wang S, Miao Z, Yang Q, Wang Y, Zhang J (2018) The dynamic roles of mesenchymal stem cells in colon cancer. Can J Gastroenterol Hepatol 2018:1–8

    Google Scholar 

  104. Gao H, Priebe W, Glod J, Banerjee D (2009) Activation of signal transducers and activators of transcription 3 and focal adhesion kinase by stromal cell-derived factor 1 is required for migration of human mesenchymal stem cells in response to tumor cell-conditioned medium. Stem Cells 27:857–865

    Article  CAS  Google Scholar 

  105. Zhang J, Lu Y, Pienta KJ (2010) Multiple roles of chemokine (C-C motif) ligand 2 in promoting prostate cancer growth. J Natl Cancer Inst 102:522–528

    Article  CAS  Google Scholar 

  106. Chanmee T, Ontong P, Konno K, Itano N (2014) Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel) 6:1670–1690

    Article  CAS  Google Scholar 

  107. Cabarcas SM, Mathews LA, Farrar WL (2011) The cancer stem cell niche – there goes the neighborhood? Int J Cancer 129:2315–2327

    Article  CAS  Google Scholar 

  108. Davis H, Irshad S, Bansal M, Rafferty H, Boitsova T, Bardella C et al (2015) Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche. Nat Med 21:62–70

    Article  CAS  Google Scholar 

  109. Kalluri R, Zeisberg M (2006) Fibroblasts in cancer. Nat Rev Cancer 6:392–401

    Article  CAS  Google Scholar 

  110. Nwabo KAH, Kamga PT, Simo RT, Vecchio L, Seke EPF, Muller JM et al (2017) Mesenchymal stromal cells’ role in tumor microenvironment: involvement of signaling pathways. Cancer Biol Med 14:129

    Article  CAS  Google Scholar 

  111. Orecchioni S, Gregato G, Martin-Padura I, Reggiani F, Braidotti P, Mancuso P et al (2013) Complementary populations of human adipose CD34+ progenitor cells promote growth, angiogenesis, and metastasis of breast cancer. Cancer Res 73:5880–5891

    Article  CAS  Google Scholar 

  112. Schwitalla S, Fingerle AA, Cammareri P, Nebelsiek T, Göktuna SI, Ziegler PK et al (2013) Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell 152:25–38

    Article  CAS  Google Scholar 

  113. Ebos JML, Kerbel RS (2011) Antiangiogenic therapy: impact on invasion, disease progression, and metastasis. Nat Rev Clin Oncol 8:210–221

    Article  CAS  Google Scholar 

  114. Ding L, Ni J, Yang F, Huang L, Deng H, Wu Y et al (2017) Promising therapeutic role of miR-27b in tumor. Tumor Biol 39:101042831769165

    Article  CAS  Google Scholar 

  115. Liu Q, Cao P (2015) Clinical and prognostic significance of HIF-1α in glioma patients: a meta-analysis. Int J Clin Exp Med 8:22073–22083

    CAS  Google Scholar 

  116. Li J, Xu J, Yan X, Jin K, Li W, Zhang R (2018) Targeting interleukin-6 (IL-6) sensitizes anti-PD-L1 treatment in a colorectal cancer preclinical model. Med Sci Monit 24:5501–5508

    Article  CAS  Google Scholar 

  117. Kampan NC, Xiang SD, McNally OM, Stephens AN, Quinn MA, Plebanski M (2018) Immunotherapeutic interleukin-6 or interleukin-6 receptor blockade in cancer: challenges and opportunities. Curr Med Chem 25:4785–4806

    Article  CAS  Google Scholar 

  118. Alfaro C, Sanmamed MF, Rodríguez-Ruiz ME, Teijeira Á, Oñate C, González Á et al (2017) Interleukin-8 in cancer pathogenesis, treatment and follow-up. Cancer Treat Rev 60:24–31

    Article  CAS  Google Scholar 

  119. Papaccio F, Della Corte C, Viscardi G, Di Liello R, Esposito G, Sparano F et al (2018) HGF/MET and the immune system: relevance for cancer immunotherapy. Int J Mol Sci 19:3595

    Article  CAS  Google Scholar 

  120. Colak S, ten Dijke P (2017) Targeting TGF-β signaling in cancer. Trends Cancer 3:56–71

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work has been partially funded by the Ministerio de Economía y Competitividad (MINECO, FEDER funds, grant numbers MAT2015-62644.C2.2.R and RTI2018-101309-B-C22), the Consejería de Economía, Conocimiento, Empresas y Universidad de la Junta de Andalucía (European Regional Development Fund (ERDF), ref. SOMM17/6109/UGR), grants from the Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (FEDER funds, projects no. PIE16/00045 and DTS17/00087), and from the Chair “Doctors Galera-Requena in cancer stem cell research” (CMC-CTS963).

Conflicts of Interest

None of the authors have a conflict of interest to declare.

Author information

Authors and Affiliations

  1. Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, Granada, Spain

    Gema Jiménez, Julia López de Andrés & Juan Antonio Marchal

  2. Instituto de Investigación Biosanitaria ibs.GRANADA, University Hospitals of Granada-University of Granada, Granada, Spain

    Gema Jiménez, Julia López de Andrés & Juan Antonio Marchal

  3. Excellence Research Unit “Modeling Nature” (MNat), University of Granada, Granada, Spain

    Gema Jiménez, Julia López de Andrés & Juan Antonio Marchal

  4. Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain

    Juan Antonio Marchal

Authors
  1. Gema Jiménez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Julia López de Andrés
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Juan Antonio Marchal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Gema Jiménez or Juan Antonio Marchal .

Editor information

Editors and Affiliations

  1. Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Alexander Birbrair

Rights and permissions

Reprints and permissions

Copyright information

© 2020 The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Jiménez, G., López de Andrés, J., Marchal, J.A. (2020). Stem Cell-Secreted Factors in the Tumor Microenvironment. In: Birbrair, A. (eds) Tumor Microenvironment . Advances in Experimental Medicine and Biology, vol 1277. Springer, Cham. https://doi.org/10.1007/978-3-030-50224-9_8

Download citation

Publish with us

Policies and ethics

Search

Navigation