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Critical Roles of Stromal Fibroblasts in the Cancer Microenvironments

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Tumor-Associated Fibroblasts and their Matrix

Part of the book series: The Tumor Microenvironment ((TTME,volume 4))

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Abstract

This review summarizes current research defining the intricate relationship between tumor and stroma with special emphasis on the origin of stromal fibroblasts, their heterogeneity, and their co-evolution with cancer epithelium. The concept of co-targeting tumor and stroma and the opportunity to develop clinical biomarkers for predictive oncology are discussed. Finally, recent investigations of the pluripotent and multi-potent properties of embryonic and adult stem and mesenchymal cells expand our understanding of the diverse ways stromal fibroblasts contribute to prostate cancer growth and progression.

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References

  • Anastasiadis AG, Bemis DL, Stisser BC, Salomon L, Ghafar MA, Buttyan R (2003) Tumor cell hypoxia and the hypoxia-response signaling system as a target for prostate cancer therapy. Curr Drug Targets 4(3):191–196

    Article  PubMed  CAS  Google Scholar 

  • Araujo J, Logothetis C (2009) Targeting Src signaling in metastatic bone disease. Int J Cancer 124(1):1–6

    Article  PubMed  CAS  Google Scholar 

  • Armant DR (2005) Blastocysts don’t go it alone. Extrinsic signals fine-tune the intrinsic developmental program of trophoblast cells. Dev Biol 280(2):260–280

    Article  PubMed  CAS  Google Scholar 

  • Azad MB, Chen Y, Gibson SB (2009) Regulation of autophagy by reactive oxygen species (ROS): implications for cancer progression and treatment. Antioxid Redox Signal 11(4):777–790

    Article  PubMed  CAS  Google Scholar 

  • Bander NH et al (2005) Phase I trial of 177-lutetium-labeled J591, a monoclonal antibody to prostate-specific membrane antigen, in patients with androgen-independent prostate cancer. J Clin Oncol 23:4591–4601

    Article  PubMed  CAS  Google Scholar 

  • Birchmeier C, Birchmeier W, Brand-Saberi B (1996) Epithelial-mesenchymal transitions in cancer progression. Acta Anat (Basel) 156(3):217–226

    Article  CAS  Google Scholar 

  • Bonaccorsi L, Muratori M, Marchiani S, Forti G, Baldi E (2006) The androgen receptor and prostate cancer invasion. Mol Cell Endocrinol 246(1–2):157–162

    Article  PubMed  CAS  Google Scholar 

  • Buckle CH, Neville-Webbe HL, Croucher PI, Lawson MA (2010) Targeting RANK/RANKL in the treatment of solid tumours and myeloma. Curr Pharm Des 16(11):1272–1283

    Article  Google Scholar 

  • Chantrain CF, Feron O, Marbaix E, Declerck YA (2008) Bone marrow microenvironment and tumor progression. Cancer Microenviron 1(1):23–35

    Article  PubMed  CAS  Google Scholar 

  • Chiarugi P, Giannoni E (2005) Anchorage-dependent cell growth: tyrosine kinases and phosphatases meet redox regulation. Antioxid Redox Signal 7(5–6):578–592

    Article  PubMed  CAS  Google Scholar 

  • Cho HJ, Lee CS, Kwon YW et al (2010) Induction of pluripotent stem cells from adult somatic cells by protein-based reprogramming without genetic manipulation. Blood 116(3):386–395

    Google Scholar 

  • Chung LW (1993) Implications of stromal-epithelial interaction in human prostate cancer growth, progression and differentiation. Semin Cancer Biol 4(3):183–192

    PubMed  CAS  Google Scholar 

  • Chung LW (1995) The role of stromal-epithelial interaction in normal and malignant growth. Cancer Surv 23:33–42

    PubMed  CAS  Google Scholar 

  • Chung LW, Baseman A, Assikis V, Zhau HE (2005) Molecular insights into prostate cancer progression: the missing link of tumor microenvironment. J Urol 173(1):10–20

    Article  PubMed  Google Scholar 

  • Chung LW, Huang WC, Sung SY et al (2006) Stromal-epithelial interaction in prostate cancer progression. Clin Genitourin Cancer 5(2):162–170

    Article  PubMed  Google Scholar 

  • Cooper CR, Chay CH, Gendernalik JD et al (2003) Stromal factors involved in prostate carcinoma metastasis to bone. Cancer 97(Suppl 3):739–747

    Article  PubMed  CAS  Google Scholar 

  • Cress AE, Mohla S (2004) Therapeutic targeting of prostate cancer. Cancer Biol Ther 3(10):1028–1030

    Article  PubMed  Google Scholar 

  • Cushing MC, Mariner PD, Liao JT, Sims EA, Anseth KS (2008) Fibroblast growth factor represses Smad-mediated myofibroblast activation in aortic valvular interstitial cells. Faseb J 22(6):1769–1777

    Article  PubMed  CAS  Google Scholar 

  • Dakhova O, Ozen M, Creighton CJ et al (2009) Global gene expression analysis of reactive stroma in prostate cancer. Clin Cancer Res 15(12):3979–3989

    Article  PubMed  CAS  Google Scholar 

  • David KA et al (2006) Clinical utility of radiolabeled antibodies in prostate cancer. Clin Genitourin Cancer 4:249–256

    Article  PubMed  CAS  Google Scholar 

  • Desgrosellier JS, Cheresh DA (2010) Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 10(1):9–22

    Article  PubMed  CAS  Google Scholar 

  • Franco OE, Shaw AK, Strand DW, Hayward SW (2010) Cancer associated fibroblasts in cancer pathogenesis. Semin Cell Dev Biol 21(1):33–39

    Article  PubMed  CAS  Google Scholar 

  • Friedman R, Gelfand T, Weiss DW, Doljanski F (1984) Patterns of fibronectin deposition in normal and neoplastic fibroblasts and mammary tissue. Int J Tissue React 6(4):291–301

    PubMed  CAS  Google Scholar 

  • Garber K (2005) IGF-1: old growth factor shines as new drug target. J Natl Cancer Inst 97(11):790–792

    Article  PubMed  CAS  Google Scholar 

  • Garber K (2009) Companies waver in efforts to target transforming growth factor in cancer. J Natl Cancer Inst 101(24):1664–1667

    Article  PubMed  Google Scholar 

  • Garin-Chesa P, Old LJ, Rettig WJ (1990) Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers. Proc Natl Acad Sci U S A 87(18):7235–7239

    Article  PubMed  CAS  Google Scholar 

  • Gibbs JB (2000) Anticancer drug targets: growth factors and growth factor signaling. J Clin Invest 105(1):9–13

    Article  PubMed  CAS  Google Scholar 

  • Hill R, Song Y, Cardiff RD, Van Dyke T (2005) Selective evolution of stromal mesenchyme with p53 loss in response to epithelial tumorigenesis. Cell 123(6):1001–1011

    Article  PubMed  CAS  Google Scholar 

  • Hsieh CL, Kubo H, Chung LW (2004) Gene therapy for prostate cancer bone metastasis. Gene therapy targeting bone metastasis. Cancer Treat Res 118:231–290

    Article  PubMed  CAS  Google Scholar 

  • Huang WC, Wu D, Xie Z et al (2006) Beta2-microglobulin is a signaling and growth-promoting factor for human prostate cancer bone metastasis. Cancer Res 66(18):9108–9116

    Article  PubMed  CAS  Google Scholar 

  • Hugo H, Ackland ML, Blick T et al (2007) Epithelial–mesenchymal and mesenchymal–epithelial transitions in carcinoma progression. J Cell Physiol 213(2):374–383

    Article  PubMed  CAS  Google Scholar 

  • Ingber DE (2008) Can cancer be reversed by engineering the tumor microenvironment? Semin Cancer Biol 18(5):356–364

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa K, Koshikawa N, Takenaga K, Nakada K, Hayashi J (2008) Reversible regulation of metastasis by ROS-generating mtDNA mutations. Mitochondrion 8(4):339–344

    Article  PubMed  CAS  Google Scholar 

  • Jaganathan BG, Ruester B, Dressel L et al (2007) Rho inhibition induces migration of mesenchymal stromal cells. Stem Cells 25(8):1966–1974

    Article  PubMed  CAS  Google Scholar 

  • Tang Y, Lin CJ, Tian XC (2010) Functionality and transduction condition evaluation of recombinant klf4 for reprogramming iPS cells. Cell Reprogram 13:99–112

    Google Scholar 

  • Jiang YG, Luo Y, He DL et al (2007) Role of Wnt/beta-catenin signaling pathway in epithelial-mesenchymal transition of human prostate cancer induced by hypoxia-inducible factor-1alpha. Int J Urol 14(11):1034–1039

    Article  PubMed  CAS  Google Scholar 

  • Josson S, Matsuoka Y, Chung LW, Zhau HE, Wang, R (2010) Tumor-stroma co-evolution in prostate cancer progression and metastasis. Semin Cell Dev Biol 21(1):26–32

    Google Scholar 

  • Jung T, Castellana D, Klingbeil P et al (2009) CD44v6 dependence of premetastatic niche preparation by exosomes. Neoplasia 11(10):1093–1105

    PubMed  CAS  Google Scholar 

  • Kabashima A, Higuchi H, Takaishi H et al (2009) Side population of pancreatic cancer cells predominates in TGF-beta-mediated epithelial to mesenchymal transition and invasion. Int J Cancer 124(12):2771–2779

    Article  PubMed  CAS  Google Scholar 

  • Kaewpila S, Venkataraman S, Buettner GR, Oberley LW (2008) Manganese superoxide dismutase modulates hypoxia-inducible factor-1 alpha induction via superoxide. Cancer Res 68(8):2781–2788

    Article  PubMed  CAS  Google Scholar 

  • Kang BH, Altieri DC (2009) Compartmentalized cancer drug discovery targeting mitochondrial Hsp90 chaperones. Oncogene 28(42):3681–3688

    Article  PubMed  CAS  Google Scholar 

  • Kaplan RN, Riba RD, Zacharoulis S et al (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438(7069):820–827

    Article  PubMed  CAS  Google Scholar 

  • Kaplan RN, Psaila B, Lyden D (2007) Niche-to-niche migration of bone-marrow-derived cells. Trends Mol Med 13(2):72–81

    Article  PubMed  CAS  Google Scholar 

  • Kargozaran H, Yuan SY, Breslin JW et al (2007) A role for endothelial-derived matrix metalloproteinase-2 in breast cancer cell transmigration across the endothelial-basement membrane barrier. Clin Exp Metastasis 24(7):495–502

    Article  PubMed  CAS  Google Scholar 

  • Karnoub AE, Dash AB, Vo AP et al (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449(7162):557–563

    Article  PubMed  CAS  Google Scholar 

  • Keller ET (2002) The role of osteoclastic activity in prostate cancer skeletal metastases. Drugs Today (Barc) 38(2):91–102

    Article  CAS  Google Scholar 

  • Kennard S, Liu H, Lilly B (2008) Transforming growth factor-beta (TGF-1) down-regulates Notch3 in fibroblasts to pro0mote smooth muscle gene expression. J Biol Chem 283(3):1324–1333

    Article  PubMed  CAS  Google Scholar 

  • Kikuta K, Masamune A, Satoh M, Suzuki N, Satoh K, Shimosegawa T (2006) Hydrogen peroxide activates activator protein-1 and mitogen-activated protein kinases in pancreatic stellate cells. Mol Cell Biochem 291(1–2):11–20

    Article  PubMed  CAS  Google Scholar 

  • Klymkowsky MW, Savagner P (2009) Epithelial-mesenchymal transition: a cancer researcher’s conceptual friend and foe. Am J Pathol 174(5):1588–1593

    Article  PubMed  CAS  Google Scholar 

  • Kopetz ES, Nelson JB, Carducci MA (2002) Endothelin-1 as a target for therapeutic intervention in prostate cancer. Invest New Drugs 20(2):173–182

    Article  PubMed  CAS  Google Scholar 

  • Kubo H, Gardner TA, Wada Y et al (2003) Phase I dose escalation clinical trial of adenovirus vector carrying osteocalcin promoter-driven herpes simplex virus thymidine kinase in localized and metastatic hormone-refractory prostate cancer. Hum Gene Ther 14(3):227–241

    Article  PubMed  CAS  Google Scholar 

  • Lalich M et al (2007) Endothelin receptor antagonists in cancer therapy. Cancer Invest 25(8):785–794

    Article  PubMed  CAS  Google Scholar 

  • Leber MF, Efferth T (2009) Molecular principles of cancer invasion and metastasis (review). Int J Oncol 34(4):881–895

    PubMed  CAS  Google Scholar 

  • Liegibel UM, Sommer U, Tomakidi P et al (2002) Concerted action of androgens and mechanical strain shifts bone metabolism from high turnover into an osteoanabolic mode. J Exp Med 196(10):1387–1392

    Article  PubMed  CAS  Google Scholar 

  • Malins DC, Anderson KM, Jaruga P et al (2006) Oxidative changes in the DNA of stroma and epithelium from the female breast: potential implications for breast cancer. Cell Cycle 5(15):1629–1632

    Article  PubMed  CAS  Google Scholar 

  • Martin FT, Dwyer RM, Kelly J 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  PubMed  CAS  Google Scholar 

  • McKeithen D, Graham T, Chung LW, Odero-Marah V (2010) Snail transcription factor regulates neuroendocrine differentiation in LNCaP prostate cancer cells. Prostate 70(9):982–992

    Google Scholar 

  • McNeal JE (1978) Origin and evolution of benign prostatic enlargement. Invest Urol 15(4):340–345

    PubMed  CAS  Google Scholar 

  • Milowsky MI et al (2004) Phase I trial of 90Y-Labeled anti-PSMA monoclonal antibody J591 for androgen-independent prostate cancer. J Clin Oncol 22:2522–2531

    Article  PubMed  CAS  Google Scholar 

  • Mizutani K, Sud S, McGregor NA et al (2009) The chemokine CCL2 increases prostate tumor growth and bone metastasis through macrophage and osteoclast recruitment. Neoplasia 11(11):1235–1242

    PubMed  CAS  Google Scholar 

  • Moen I, Oyan AM, Kalland KH et al (2009) Hyperoxic treatment induces mesenchymal-to-epithelial transition in a rat adenocarcinoma model. PLoS One 4(7):e6381

    Article  PubMed  CAS  Google Scholar 

  • Molloy AP, Martin FT, Dwyer RM et al (2009) Mesenchymal stem cell secretion of chemokines during differentiation into osteoblasts, and their potential role in mediating interactions with breast cancer cells. Int J Cancer 124(2):326–332

    Article  PubMed  CAS  Google Scholar 

  • Mueller MM, Fusenig NE (2004) Friends or foes—bipolar effects of the tumour stroma in cancer. Nat Rev Cancer 4(11):839–849

    Article  PubMed  CAS  Google Scholar 

  • Nilsson S, Larsen RH, Fossa SD et al (2005) First clinical experience with alpha-emitting radium-223 in the treatment of skeletal metastases. Clin Cancer Res 11(12):4451–4459

    Article  PubMed  CAS  Google Scholar 

  • Nilsson S, Franzen L, Parker C et al (2007) Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study. Lancet Oncol 8(7):587–594

    Article  PubMed  CAS  Google Scholar 

  • Okita K, Ichisaka T, Yamanaka, S (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448(7151):313–317

    Article  PubMed  CAS  Google Scholar 

  • Olapade-Olaopa EO, MacKay EH, Taub NA, Sandhu DP, Terry TR, Habib FK (1999) Malignant transformation of human prostatic epithelium is associated with the loss of androgen receptor immunoreactivity in the surrounding stroma. Clin Cancer Res 5(3):569–576

    PubMed  CAS  Google Scholar 

  • Olaso E, Salado C, Egilegor E et al (2003) Proangiogenic role of tumor-activated hepatic stellate cells in experimental melanoma metastasis. Hepatology 37(3):674–685

    Article  PubMed  CAS  Google Scholar 

  • Park SM, Gaur AB, Lengyel E, Peter ME (2008) The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev 22(7):894–907

    Article  PubMed  CAS  Google Scholar 

  • Pathak S, Nemeth MA, Multani AS, Thalmann GN, von Eschenbach AC, Chung LW (1997) Can cancer cells transform normal host cells into malignant cells? Br J Cancer 76(9):1134–1138

    Article  PubMed  CAS  Google Scholar 

  • Pollard JW (2009) Trophic macrophages in development and disease. Nat Rev Immunol 9(4):259–270

    Article  PubMed  CAS  Google Scholar 

  • Pontier SM, Muller WJ (2009) Integrins in mammary-stem-cell biology and breast-cancer progression—a role in cancer stem cells? J Cell Sci 122(Pt 2):207–214

    Article  PubMed  CAS  Google Scholar 

  • Ponzo MG, Lesurf R, Petkiewicz S et al (2009) Met induces mammary tumors with diverse histologies and is associated with poor outcome and human basal breast cancer. Proc Natl Acad Sci U S A 106(31):12903–12908

    Article  PubMed  CAS  Google Scholar 

  • Prindull G (2005) Hypothesis: cell plasticity, linking embryonal stem cells to adult stem cell reservoirs and metastatic cancer cells? Exp Hematol 33(7):738–746

    Article  PubMed  CAS  Google Scholar 

  • Radisky DC, Przybylo JA (2008) Matrix metalloproteinase-induced fibrosis and malignancy in breast and lung. Proc Am Thorac Soc 5(3):316–322

    Article  PubMed  CAS  Google Scholar 

  • Rhee HW, Zhau HE, Pathak S et al (2001) Permanent phenotypic and genotypic changes of prostate cancer cells cultured in a three-dimensional rotating-wall vessel. In Vitro Cell Dev Biol Anim 37(3):127–140

    Article  PubMed  CAS  Google Scholar 

  • Rhee YH, Ko JY, Chang MY et al (2011) Protein-based human iPS cells efficiently generate functional dopamine neurons and can treat a rat model of Parkinson disease. J Clin Invest 121(6):2326–2335

    Google Scholar 

  • Rhodes LV, Muir SE, Elliott S et al (2009) Adult human mesenchymal stem cells enhance breast tumorigenesis and promote hormone independence. Breast Cancer Res Treat 113:293–299

    Google Scholar 

  • Ronnov-Jessen L, Bissell MJ (2009) Breast cancer by proxy: can the microenvironment be both the cause and consequence? Trends Mol Med 15(1):5–13

    Article  PubMed  CAS  Google Scholar 

  • Roorda BD, ter Elst A, Kamps WA, de Bont ES (2009) Bone marrow-derived cells and tumor growth: contribution of bone marrow-derived cells to tumor micro-environments with special focus on mesenchymal stem cells. Crit Rev Oncol Hematol 69(3):187–198

    Article  PubMed  Google Scholar 

  • Saad F, Abrahamsson PA, Miller K (2009) Preserving bone health in patients with hormone-sensitive prostate cancer: the role of bisphosphonates. BJU Int 104(11):1573–1579

    Article  PubMed  CAS  Google Scholar 

  • Sabbah M, Emami S, Redeuilh G et al (2008) Molecular signature and therapeutic perspective of the epithelial-to-mesenchymal transitions in epithelial cancers. Drug Resist Updat 11(4–5):123–151

    Article  PubMed  CAS  Google Scholar 

  • Sangaletti S, Di Carlo E, Gariboldi S et al (2008) Macrophage-derived SPARC bridges tumor cell-extracellular matrix interactions toward metastasis. Cancer Res 68(21):9050–9059

    Article  PubMed  CAS  Google Scholar 

  • Santamaria-Martinez A, Barquinero J, Barbosa-Desongles A et al (2009) Identification of multipotent mesenchymal stromal cells in the reactive stroma of a prostate cancer xenograft by side population analysis. Exp Cell Res 315(17):3004–3013

    Article  PubMed  CAS  Google Scholar 

  • Sartor O (2009) Radiopharmaceutical and chemotherapy combinations in metastatic castrate-resistant prostate cancer: a new beginning? J Clin Oncol 27(15):2417–2418

    Article  PubMed  Google Scholar 

  • Singh S, Singh R, Singh UP et al (2009) Clinical and biological significance of CXCR5 expressed by prostate cancer specimens and cell lines. Int J Cancer 125(10):2288–2295

    Article  PubMed  CAS  Google Scholar 

  • Spaeth E, Klopp A, Dembinski J, Andreeff M, Marini F (2008) Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells. Gene Ther 15(10):730–738

    Article  PubMed  CAS  Google Scholar 

  • Stupp R et al (2007) Integrin inhibitors reaching the clinic. J Clin Oncol 25:1637–1638

    Article  PubMed  CAS  Google Scholar 

  • Sung SY, Kubo H, Shigemura K et al (2006) Oxidative stress induces ADAM9 protein expression in human prostate cancer cells. Cancer Res 66(19):9519–9526

    Article  PubMed  CAS  Google Scholar 

  • Sung SY, Hsieh CL, Law A et al (2008) Coevolution of prostate cancer and bone stroma in three-dimensional coculture: implications for cancer growth and metastasis. Cancer Res 68(23):9996–10003

    Article  PubMed  CAS  Google Scholar 

  • Svineng G, Ravuri C, Rikardsen O, Huseby NE, Winberg JO (2008) The role of reactive oxygen species in integrin and matrix metalloproteinase expression and function. Connect Tissue Res 49(3):197–202

    Article  PubMed  CAS  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676

    Article  PubMed  CAS  Google Scholar 

  • Tasseff R, Nayak S, Salim S, Kaushik P, Rizvi N, Varner JD (2010) Analysis of the molecular networks in androgen dependent and independent prostate cancer revealed fragile and robust subsystems. PLoS One 5(1):e8864

    Article  PubMed  CAS  Google Scholar 

  • Thalmann GN, Anezinis PE, Chang SM et al (1994) Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer. Cancer Res 54(10):2577–2581

    PubMed  CAS  Google Scholar 

  • Thalmann GN, Rhee H, Sikes RA et al (2009) Human prostate fibroblasts induce growth and confer castration resistance and metastatic potential in LNCaP cells. Eur Urol 58:162–172.

    Google Scholar 

  • Tothill RW, Tinker AV, George J et al (2008) Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clin Cancer Res 14(16):5198–5208

    Article  PubMed  CAS  Google Scholar 

  • Trikha M et al (2004) CNTO 95, a fully human monoclonal antibody that inhibits alphav integrins, has antitumor and antiangiogenic activity in vivo. Int J Cancer 110(3):326–335

    Article  PubMed  CAS  Google Scholar 

  • Tu SM, Lin SH (2008) Current trials using bone-targeting agents in prostate cancer. Cancer J 14(1):35–39

    Article  PubMed  CAS  Google Scholar 

  • Tu SM, Kim J, Pagliaro LC et al (2005) Therapy tolerance in selected patients with androgen-independent prostate cancer following strontium-89 combined with chemotherapy. J Clin Oncol 23(31):7904–7910

    Article  PubMed  CAS  Google Scholar 

  • Tuxhorn JA, Ayala GE, Rowley DR (2001) Reactive stroma in prostate cancer progression. J Urol 166(6):2472–2483

    Article  PubMed  CAS  Google Scholar 

  • Tuxhorn JA, Ayala GE, Smith MJ, Smith VC, Dang TD, Rowley DR (2002) Reactive stroma in human prostate cancer: induction of myofibroblast phenotype and extracellular matrix remodeling. Clin Cancer Res 8(9):2912–2923

    PubMed  CAS  Google Scholar 

  • Untergasser G, Gander R, Lilg C, Lepperdinger G, Plas E, Berger P (2005) Profiling molecular targets of TGF-beta1 in prostate fibroblast-to-myofibroblast transdifferentiation. Mech Ageing Dev 126(1):59–69

    Article  PubMed  CAS  Google Scholar 

  • Vessella RL, Corey E (2006) Targeting factors involved in bone remodeling as treatment strategies in prostate cancer bone metastasis. Clin Cancer Res 12(20 Pt 2):6285s–6290s

    Article  Google Scholar 

  • Wang M, Kirk JS, Venkataraman S et al (2005) Manganese superoxide dismutase suppresses hypoxic induction of hypoxia-inducible factor-1alpha and vascular endothelial growth factor. Oncogene 24(55):8154–8166

    PubMed  CAS  Google Scholar 

  • Wells A, Yates C, Shepard CR (2008) E-cadherin as an indicator of mesenchymal to epithelial reverting transitions during the metastatic seeding of disseminated carcinomas. Clin Exp Metastasis 25(6):621–628

    Article  PubMed  CAS  Google Scholar 

  • Wu JD, Odman A, Higgins LM et al (2005) In vivo effects of the human type I insulin-like growth factor receptor antibody A12 on androgen-dependent and androgen-independent xenograft human prostate tumors. Clin Cancer Res 11(8):3065–3074

    Article  PubMed  CAS  Google Scholar 

  • Yanagisawa N, Li R, Rowley D et al (2007) Stromogenic prostatic carcinoma pattern (carcinomas with reactive stromal grade 3) in needle biopsies predicts biochemical recurrence-free survival in patients after radical prostatectomy. Hum Pathol 38(11):1611–1620

    Article  PubMed  CAS  Google Scholar 

  • Yao Q, Qu X, Yang Q, Wei M, Kong B (2009) CLIC4 mediates TGF-beta1-induced fibroblast-to-myofibroblast transdifferentiation in ovarian cancer. Oncol Rep 22(3):541–548

    PubMed  CAS  Google Scholar 

  • Yu J, Hu K, Smuga-Otto K et al (2009) Human induced pluripotent stem cells free of vector and transgene sequences. Science 324(5928):797–801

    Article  PubMed  CAS  Google Scholar 

  • Zhao HF, Chen J, Xu ZS, Zhang KQ (2009a) Distribution and differentiation of mesenchymal stem cells in tumor tissue. Chin Med J (Engl) 122(6):712–715

    Google Scholar 

  • Zhao XY, Li W, Lv Z et al (2009b) iPS cells produce viable mice through tetraploid complementation. Nature 461(7260):86–90

    Article  CAS  Google Scholar 

  • Zhau HE, Odero-Marah V, Lue HW et al (2008) Epithelial to mesenchymal transition (EMT) in human prostate cancer: lessons learned from ARCaP model. Clin Exp Metastasis 25(6):601–610

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The author wishes to thank Dr. Sajni Josson for her help in the construction of the figure and the table. The editorial assistance from Gary Mawyer is also appreciated. This work was supported in part by the following grants: R01 CA122602 and P01 CA098912 from National Caner Institute and W81 XWH-01–1-0172 from Department of Defense, United States Army.

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  1. Uro-Oncology Research Program, Departments of Medicine and Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center and the University of California, 90048, Los Angeles, CA, USA

    Leland W. K. Chung

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Correspondence to Leland W. K. Chung .

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  1. Siederstrasse 13, Villingen-Schwenningen, 78054, Germany

    Margareta M. Mueller

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    Norbert E. Fusenig

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Chung, L.W. (2011). Critical Roles of Stromal Fibroblasts in the Cancer Microenvironments. In: Mueller, M., Fusenig, N. (eds) Tumor-Associated Fibroblasts and their Matrix. The Tumor Microenvironment, vol 4. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0659-0_1

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