Skip to main content

The Participation of Mesenchymal Stem Cells in Tumor Stroma Formation and Their Application as Targeted-Gene Delivery Vehicles

  • Chapter
Bone Marrow-Derived Progenitors

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 180))

Abstract

Recent evidence suggests that mesenchymal stem cells (MSC) selectively proliferate to tumors and contribute to the formation of tumor-associated stroma. The biological rationale for tumor recruitment of MSC remains unclear but may represent an effort of the host to blunt tumor cell growth and improve survival. There is mounting experimental evidence that normal stromal cells can revert malignant cell behavior, and separate studies have demonstrated that stromal cells can enhance tumor progression after acquisition of tumor-like genetic lesions. Together, these observations support the rationale for modifying normal MSC to deliver therapeutic proteins directly into the tumor microenvironment. Modified MSC can produce high concentrations of antitumor proteins directly within the Tumor mass, which have been shown to blunt tumor growth kinetics in experimental animal model systems. In this chapter we will address the biological properties of MSC within the tumor microenvironment and discuss the potential use of MSC and other bone marrow-derived cell populations as delivery vehicles for antitumor proteins.

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

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  • Allers C, Sierralta WD, Neubauer S, Rivera F, Minguell JJ, Conget PA (2004) Dynamic of distribution of human bone marrow-derived mesenchymal stem cells after transplantation into adult unconditioned mice. Transplantation 78:503–508

    PubMed  Google Scholar 

  • Almeida-Porada G, Porada C, Zanjani ED (2004) Plasticity of human stem cells in the fetal sheep model of human stem cell transplantation. Int J Hematol 79:1–6

    PubMed  Google Scholar 

  • Baksh D, Song L, Tuan RS (2004) Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med 8:301–316

    PubMed  CAS  Google Scholar 

  • Ballas CB, Zielske SP, Gerson SL (2002) Adult bone marrow stem cells for cell and gene therapies: implications for greater use. J Cell Biochem Suppl 38:20–28

    PubMed  Google Scholar 

  • Bang OY, Lee JS, Lee PH, Lee G (2005) Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 57:874–882

    PubMed  Google Scholar 

  • Barcellos-Hoff MH, Ravani SA (2000) Irradiated mammary gland stroma promotes the expression of tumorigenic potential by unirradiated epithelial cells. Cancer Res 60:1254–1260

    PubMed  CAS  Google Scholar 

  • Bianchi G, Muraglia A, Daga A, Corte G, Cancedda R, Quarto R (2001) Microenvironment and stem properties of bone marrow-derived mesenchymal cells. Wound Repair Regen 9:460–466

    PubMed  CAS  Google Scholar 

  • Bissell MJ, Labarge MA (2005) Context, tissue plasticity, and cancer: are tumor stem cells also regulated by the microenvironment? Cancer Cell 7:17–23

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Burns JS, Abdallah BM, Guldberg P, Rygaard J, Schroder HD, Kassem M (2005) Tumorigenic heterogeneity in cancer stem cells evolved from long-term cultures of telomerase-immortalized human mesenchymal stem cells. Cancer Res 65:3126–3135

    PubMed  CAS  Google Scholar 

  • Burns MJ, Weiss W (2003) Targeted therapy of brain tumors utilizing neural stem and progenitor cells. Front Biosci 8:e228–234

    PubMed  Google Scholar 

  • Caplan AI, Bruder SP (2001) Mesenchymal stem cells: building blocks for molecular medicine in the 21st century. Trends Mol Med 7:259–264

    PubMed  CAS  Google Scholar 

  • Chan J, O’Donoghue K, de la Fuente J, et al (2005) Human fetal mesenchymal stem cells as vehicles for gene delivery. Stem Cells 23:93–102

    PubMed  CAS  Google Scholar 

  • Chen J, Wang C, Lu S, et al (2005) In vivo chondrogenesis of adult bone-marrow-derived autologous mesenchymal stem cells. Cell Tissue Res 319:429–438

    PubMed  Google Scholar 

  • Chen SL, Fang WW, Ye F, et al (2004) Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol 94:92–95

    PubMed  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 173:10–20

    PubMed  Google Scholar 

  • Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867

    PubMed  CAS  Google Scholar 

  • Cunha GR, Hom YK (1996) Role of mesenchymal-epithelial interactions in mammary gland development. J Mammary Gland Biol Neoplasia 1:21–35

    PubMed  CAS  Google Scholar 

  • Cunha GR, Hayward SW, Wang YZ, Ricke WA (2003) Role of the stromal microenvironment in carcinogenesis of the prostate. Int J Cancer 107:1–10

    PubMed  CAS  Google Scholar 

  • Dai W, Hale SL, Martin BJ, et al (2005) Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium: short-and long-term effects. Circulation 112:214–223

    PubMed  Google Scholar 

  • De Kok IJ, Drapeau SJ, Young R, Cooper LF (2005) Evaluation of mesenchymal stem cells following implantation in alveolar sockets: a canine safety study. Int J Oral Maxillofac Implants 20:511–518

    PubMed  Google Scholar 

  • De Palma M, Venneri MA, Roca C, Naldini L (2003) Targeting exogenous genes to tumor angiogenesis by transplantation of genetically modified hematopoietic stem cells. Nat Med 9:789–795

    PubMed  Google Scholar 

  • De Palma M, Venneri MA, Galli R, et al (2005) Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 8:211–226

    PubMed  Google Scholar 

  • De Wever O, Mareel M (2003) Role of tissue stroma in cancer cell invasion. J Pathol 200:429–447

    PubMed  Google Scholar 

  • Deans RJ, Moseley AB (2000) Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol 28:875–884

    PubMed  CAS  Google Scholar 

  • Dennis JE, Cohen N, Goldberg VM, Caplan AI (2004) Targeted delivery of progenitor cells for cartilage repair. J Orthop Res 22:735–741

    PubMed  CAS  Google Scholar 

  • Devine SM, Cobbs C, Jennings M, Bartholomew A, Hoffman R (2003) Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates. Blood 101:2999–3001

    PubMed  CAS  Google Scholar 

  • Direkze NC, Forbes SJ, Brittan M, et al (2003) Multiple organ engraftment by bone-marrow-derived myofibroblasts and fibroblasts in bone-marrow-transplanted mice. Stem Cells 21:514–520

    PubMed  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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Dong J, Grunstein J, Tejada M, et al (2004) VEGF-null cells require PDGFR alpha signaling-mediated stromal fibroblast recruitment for tumorigenesis. EMBO J 23:2800–2810

    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

    PubMed  CAS  Google Scholar 

  • Emura M, Ochiai A, Horino M, Arndt W, Kamino K, Hirohashi S (2000) Development of myofibroblasts from human bone marrow mesenchymal stem cells cocultured with human colon carcinoma cells and TGF beta 1. In Vitro Cell Dev Biol Anim 36:77–80

    PubMed  CAS  Google Scholar 

  • Erices AA, Allers CI, Conget PA, Rojas CV, Minguell JJ (2003) Human cord blood-derived mesenchymal stem cells home and survive in them arrow of immunodeficient mice after systemic infusion. Cell Transplant 12:555–561

    PubMed  Google Scholar 

  • Evans CH, Robbins PD, Ghivizzani SC, et al (2005) Gene transfer to human joints: progress toward a gene therapy of arthritis. Proc Natl Acad Sci U S A 102:8698–8703

    PubMed  CAS  Google Scholar 

  • Feldmann RE Jr, Bieback K, Maurer MH, et al (2005) Stem cell proteomes: a profile of human mesenchymal stem cells derived from umbilical cord blood. Electrophoresis 26:2749–2758

    PubMed  CAS  Google Scholar 

  • Fiedler J, Etzel N, Brenner RE (2004) To go or not to go: migration of human mesenchymal progenitor cells stimulated by isoforms of PDGF. J Cell Biochem 93:990–998

    PubMed  CAS  Google Scholar 

  • Fierro FA, Sierralta WD, Epunan MJ, Minguell JJ (2004)Marrow-derived mesenchymal stem cells: role in epithelial tumor cell determination. Clin Exp Metastasis 21:313–319

    PubMed  CAS  Google Scholar 

  • Folkman J (2003) Fundamental concepts of the angiogenic process. Curr Mol Med 3:643–651

    PubMed  CAS  Google Scholar 

  • Folkman J (2004) Endogenous angiogenesis inhibitors. Apmis 112:496–507

    PubMed  CAS  Google Scholar 

  • Forbes SJ, Russo FP, Rey V, et al (2004) A significant proportion of myofibroblasts are of bone marrow origin in human liver fibrosis. Gastroenterology 126:955–963

    PubMed  Google Scholar 

  • Forte G, Minieri M, Cossa P, et al (2006) Hepatocyte growth factor effects on mesenchymal stem cells: proliferation, migration, and differentiation. Stem Cells 24:23–33

    PubMed  CAS  Google Scholar 

  • Fukuda K (2003) Use of adult marrow mesenchymal stem cells for regeneration of cardiomyocytes. Bone Marrow Transplant 32[Suppl 1]:S25–27

    PubMed  CAS  Google Scholar 

  • Gallego MI, Binart N, Robinson GW, et al (2001) Prolactin, growth hormone, and epidermal growth factor activate Stat5 in different compartments of mammary tissue and exert different and overlapping developmental effects. Dev Biol 229:163–175

    PubMed  CAS  Google Scholar 

  • Garcia-Olmo D, Garcia-Arranz M, Herreros D, Pascual I, Peiro C, Rodriguez-Montes JA (2005) A phase I clinical trial of the treatment of Crohn’s fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum 48:1416–1423

    PubMed  Google Scholar 

  • Gojo S, Umezawa A (2003) Plasticity of mesenchymal stem cells-regenerative medicine for diseased hearts. Hum Cell 16:23–30

    PubMed  Google Scholar 

  • Gronthos S, Zannettino AC, Hay SJ, et al (2003) Molecular and cellular characterisation of highly purified stromal stem cells derived from human bone marrow. J Cell Sci 116:1827–1835

    PubMed  CAS  Google Scholar 

  • Haffen K, Kedinger M, Simon-Assmann P (1987) Mesenchyme-dependent differentiation of epithelial progenitor cells in the gut. J Pediatr Gastroenterol Nutr 6:14–23

    PubMed  CAS  Google Scholar 

  • Hamada H, Kobune M, Nakamura K, et al (2005) Mesenchymal stem cells (MSC) as therapeutic cytoreagents for gene therapy. Cancer Sci 96:149–156

    PubMed  CAS  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    PubMed  CAS  Google Scholar 

  • Harrington K, Alvarez-Vallina L, Crittenden M, et al (2002) Cells as vehicles for cancer gene therapy: the missing link between targeted vectors and systemic delivery? Hum Gene Ther 13:1263–1280

    PubMed  CAS  Google Scholar 

  • Hasebe T, Mukai K, Tsuda H, Ochiai A (2000) New prognostic histological parameter of invasive ductal carcinoma of the breast: clinicopathological significance of fibrotic focus. Pathol Int 50:263–272

    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 123:1001–1011

    PubMed  CAS  Google Scholar 

  • Hombauer H, Minguell JJ (2000) Selective interactions between epithelial tumour cells and bone marrow mesenchymal stem cells. Br J Cancer 82:1290–1296

    PubMed  CAS  Google Scholar 

  • Honma T, Honmou O, Iihoshi S, et al (2006) Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat. Exp Neurol 199:56–66

    PubMed  CAS  Google Scholar 

  • Horwitz EM, Prockop DJ, Fitzpatrick LA, et al (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 5:309–313

    PubMed  CAS  Google Scholar 

  • Houghton J, Stoicov C, Nomura S, et al (2004) Gastric cancer originating from bone marrow-derived cells. Science 306:1568–1571

    PubMed  CAS  Google Scholar 

  • Hurwitz DR, Kirchgesser M, Merrill W, et al (1997) Systemic delivery of human growth hormone or human factor IX in dogs by reintroduced genetically modified autologous bone marrow stromal cells. Hum Gene Ther 8:137–156

    PubMed  CAS  Google Scholar 

  • Iacobuzio-Donahue CA, Argani P, Hempen PM, Jones J, Kern SE (2002) The desmoplastic response to infiltrating breast carcinoma: gene expression at the site of primary invasion and implications for comparisons between tumor types. Cancer Res 62:5351–5357

    PubMed  CAS  Google Scholar 

  • In’t Anker PS, Scherjon SA, Kleijburg-van der Keur C, et al (2004) Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells 22:1338–1345

    Google Scholar 

  • Ishii G, Sangai T, Oda T, et al (2003) Bone-marrow-derived myofibroblasts contribute to the cancer-induced stromal reaction. Biochem Biophys Res Commun 309:232–240

    PubMed  CAS  Google Scholar 

  • Ishii G, Sangai T, Ito T, et al (2005) In vivo and in vitro characterization of human fibroblasts recruited selectively into human cancer stroma. Int J Cancer 117:212–220

    PubMed  CAS  Google Scholar 

  • Jankowski K, Kucia M, Wysoczynski M, et al (2003) Both hepatocyte growth factor(HGF) and stromal-derived factor-1 regulate the metastatic behavior of human rhabdomyosarcoma cells, but only HGF enhances their resistance to radiochemotherapy. Cancer Res 63:7926–7935

    PubMed  CAS  Google Scholar 

  • Jiang H, Conrad C, Fueyo J, Gomez-Manzano C, Liu TJ (2003) Oncolytic adenoviruses for malignant glioma therapy. Front Biosci 8:d577–588

    PubMed  CAS  Google Scholar 

  • Jin H, Su J, Garmy-Susini B, Kleeman J, Varner J (2006) Integrin alpha4beta1 promotes monocyte trafficking and angiogenesis in tumors. Cancer Res 66:2146–2152

    PubMed  CAS  Google Scholar 

  • Kammertoens T, Schuler T, Blankenstein T (2005) Immunotherapy: target the stroma to hit the tumor. Trends Mol Med 11:225–231

    PubMed  CAS  Google Scholar 

  • Kan I, Melamed E, Offen D (2005) Integral therapeutic potential of bone marrow mesenchymal stem cells. Curr Drug Targets 6:31–41

    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 438:820–827

    PubMed  CAS  Google Scholar 

  • Kassem M (2004) Mesenchymal stem cells: biological characteristics and potential clinical applications. Cloning Stem Cells 6:369–374

    PubMed  CAS  Google Scholar 

  • Kenny PA, Bissell MJ (2003) Tumor reversion: correction of malignant behavior by microenvironmental cues. Int J Cancer 107:688–695

    PubMed  CAS  Google Scholar 

  • Kiaris H, Chatzistamou I, Trimis G, Frangou-Plemmenou M, Pafiti-Kondi A, Kalofoutis A (2005) Evidence for nonautonomous effect of p53 tumor suppressor in carcinogenesis. Cancer Res 65:1627–1630

    PubMed  CAS  Google Scholar 

  • Koc ON, Day J, Nieder M, Gerson SL, Lazarus HM, Krivit W (2002) Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Bone Marrow Transplant 30:215–222

    PubMed  CAS  Google Scholar 

  • Kraitchman DL, Tatsumi M, Gilson WD, et al (2005) Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction. Circulation 112:1451–1461

    PubMed  Google Scholar 

  • Kunz-Schughart LA, Knuechel R (2002a) Tumor-associated fibroblasts (part I): active stromal participants in tumor development and progression? Histol Histopathol 17:599–621

    PubMed  CAS  Google Scholar 

  • Kunz-Schughart LA, Knuechel R (2002b) Tumor-associated fibroblasts (part II): functional impact on tumor tissue. Histol Histopathol 17:623–637

    PubMed  CAS  Google Scholar 

  • Kurose K, Hoshaw-Woodard S, Adeyinka A, Lemeshow S, Watson PH, Eng C (2001) Genetic model of multi-step breast carcinogenesis involving the epithelium and stroma: clues to tumour-microenvironment interactions. Hum Mol Genet 10:1907–1913

    PubMed  CAS  Google Scholar 

  • Kurose K, Gilley K, Matsumoto S, Watson PH, Zhou XP, Eng C (2002) Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas. Nat Genet 32:355–357

    PubMed  CAS  Google Scholar 

  • Kurosumi M, Tabei T, Inoue K, et al (2003) Prognostic significance of scoring system based on histological heterogeneity of invasive ductal carcinoma for node-negative breast cancer patients. Oncol Rep 10:833–837

    PubMed  Google Scholar 

  • Kurozumi K, Nakamura K, Tamiya T, et al (2004) BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model. Mol Ther 9:189–197

    PubMed  CAS  Google Scholar 

  • Kurozumi K, Nakamura K, Tamiya T, et al (2005) Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model. Mol Ther 11:96–104

    PubMed  CAS  Google Scholar 

  • Lange C, Togel F, Ittrich H, et al (2005) Administered mesenchymal stem cells enhance recovery from ischemia/reperfusion-induced acute renal failure in rats. Kidney Int 68:1613–1617

    PubMed  Google Scholar 

  • Lazarus HM, Koc ON, Devine SM, et al (2005) Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant 11:389–398

    PubMed  Google Scholar 

  • Le Blanc K, Pittenger M (2005) Mesenchymal stem cells: progress toward promise. Cytotherapy 7:36–45

    PubMed  Google Scholar 

  • Le Blanc K, Rasmusson I, Sundberg B, et al (2004) Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 363:1439–1441

    PubMed  Google Scholar 

  • Mansilla E, Marin GH, Sturla F, et al (2005) Human mesenchymal stem cells are tolerized by mice and improve skin and spinal cord injuries. Transplant Proc 37:292–294

    PubMed  CAS  Google Scholar 

  • Mantovani A, Sozzani S, Locati M, Allavena P, Sica A (2002) Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23:549–555

    PubMed  CAS  Google Scholar 

  • McCullough KD, Coleman WB, Ricketts SL, Wilson JW, Smith GJ, Grisham JW (1998) Plasticity of the neoplastic phenotype in vivo is regulated by epigenetic factors. Proc Natl Acad Sci U S A 95:15333–15338

    PubMed  CAS  Google Scholar 

  • McNiece I, Harrington J, Turney J, Kellner J, Shpall EJ (2004) Ex vivo expansion of cord blood mononuclear cells on mesenchymal stem cells. Cytotherapy 6:311–317

    PubMed  CAS  Google Scholar 

  • Mintz B, Illmensee K (1975) Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc Natl Acad Sci U S A 72:3585–3589

    PubMed  CAS  Google Scholar 

  • Moinfar F, Man YG, Arnould L, Bratthauer GL, Ratschek M, Tavassoli FA (2000) Concurrent and independent genetic alterations in the stromal and epithelial cells of mammary carcinoma: implications for tumorigenesis. Cancer Res 60:2562–2566

    PubMed  CAS  Google Scholar 

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

    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 

  • Natsu K, Ochi M, Mochizuki Y, Hachisuka H, Yanada S, Yasunaga Y (2004) Allogeneic bone marrow-derived mesenchymal stromal cells promote the regeneration of injured skeletal muscle without differentiation into myofibers. Tissue Eng 10:1093–1112

    PubMed  CAS  Google Scholar 

  • Ohlsson LB, Varas L, Kjellman C, Edvardsen K, Lindvall M (2003) Mesenchymal progenitor cell-mediated inhibition of tumor growth in vivo and in vitro in gelatin matrix. Exp Mol Pathol 75:248–255

    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

    PubMed  CAS  Google Scholar 

  • Ortiz LA, Gambelli F, McBride C, et al (2003) Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci U S A 100:8407–8411

    PubMed  CAS  Google Scholar 

  • Parham DM (2001) Pathologic classification of rhabdomyosarcomas and correlations with molecular studies. Mod Pathol 14:506–514

    PubMed  CAS  Google Scholar 

  • Philip M, Rowley DA, Schreiber H (2004) Inflammation as a tumor promoter in cancer induction. Semin Cancer Biol 14:433–439

    PubMed  CAS  Google Scholar 

  • Phinney DG, Isakova I (2005) Plasticity and therapeutic potential of mesenchymal stem cells in the nervous system. Curr Pharm Des 11:1255–1265

    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

    PubMed  CAS  Google Scholar 

  • Polverini PJ, Leibovich SJ (1984) Induction of neovascularization in vivo and endothelial proliferation in vitro by tumor-associated macrophages. Lab Invest 51:635–642

    PubMed  CAS  Google Scholar 

  • Prindull G, Zipori D (2004) Environmental guidance of normal and tumor cell plasticity: epithelial mesenchymal transitions as a paradigm. Blood 103:2892–2899

    PubMed  CAS  Google Scholar 

  • Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276:71–74

    PubMed  CAS  Google Scholar 

  • Prockop DJ, Sekiya I, Colter DC (2001) Isolation and characterization of rapidly self-renewing stem cells from cultures of human marrow stromal cells. Cytotherapy 3:393–396

    PubMed  CAS  Google Scholar 

  • Radisky DC, Levy DD, Littlepage LE, et al (2005) Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature 436:123–127

    PubMed  CAS  Google Scholar 

  • Reyes M, Lund T, Lenvik T, Aguiar D, Koodie L, Verfaillie CM (2001) Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood 98:2615–2625

    PubMed  CAS  Google Scholar 

  • Richter G, Kruger-Krasagakes S, Hein G, et al (1993) Interleukin 10 transfected into Chinese hamster ovary cells prevents tumor growth and macrophage infiltration. Cancer Res 53:4134–4137

    PubMed  CAS  Google Scholar 

  • Robinson SC, Coussens LM (2005) Soluble mediators of inflammation during tumor development. Adv Cancer Res 93:159–187

    PubMed  CAS  Google Scholar 

  • Rojas M, Xu J, Woods CR, et al (2005) Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol 33:145–152

    PubMed  CAS  Google Scholar 

  • Roni V, Habeler W, Parenti A, et al (2003) Recruitment of human umbilical vein endothelial cells and human primary fibroblasts into experimental tumors growing in SCID mice. Exp Cell Res 287:28–38

    PubMed  CAS  Google Scholar 

  • Ronnov-Jessen L, Petersen OW, Koteliansky VE, Bissell MJ (1995) The origin of the myofibroblasts in breast cancer. Recapitulation of tumor environment in culture unravels diversity and implicates converted fibroblasts and recruited smooth muscle cells. J Clin Invest 95:859–873

    PubMed  CAS  Google Scholar 

  • Ronnov-Jessen L, Petersen OW, Bissell MJ (1996) Cellular changes involved in conversion of normal to malignant breast: importance of the stromal reaction. Physiol Rev 76:69–125

    PubMed  CAS  Google Scholar 

  • Rowley DR (1998) What might a stromal response mean to prostate cancer progression? Cancer Metastasis Rev 17:411–419

    PubMed  CAS  Google Scholar 

  • Rubio D, Garcia-Castro J, Martin MC, et al (2005) Spontaneous human adult stem cell transformation. Cancer Res 65:3035–3039

    PubMed  CAS  Google Scholar 

  • Sakakura T, Nishizuka Y, Dawe CJ (1976) Mesenchyme-dependent morphogenesis and epithelium-specific cytodifferentiation in mouse mammary gland. Science 194:1439–1441

    PubMed  CAS  Google Scholar 

  • Sangai T, Ishii G, Kodama K, et al (2005) Effect of differences in cancer cells and tumor growth sites on recruiting bone marrow-derived endothelial cells and myofibroblasts in cancer-induced stroma. Int J Cancer 115:885–892

    PubMed  CAS  Google Scholar 

  • Sato Y, Araki H, Kato J, et al (2005) Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood 106:756–763

    PubMed  CAS  Google Scholar 

  • Satoh H, Kishi K, Tanaka T, et al (2004) Transplanted mesenchymal stem cells are effective for skin regeneration in acute cutaneous wounds. Cell Transplant 13:405–412

    PubMed  Google Scholar 

  • Schoeberlein A, Holzgreve W, Dudler L, Hahn S, Surbek DV (2005) Tissue-specific engraftment after in utero transplantation of allogeneic mesenchymal stem cells into sheep fetuses. Am J Obstet Gynecol 192:1044–1052

    PubMed  CAS  Google Scholar 

  • Sekiya I, Larson BL, Smith JR, Pochampally R, Cui JG, Prockop DJ (2002) Expansion of human adult stem cells from bone marrow stroma: conditions that maximize the yields of early progenitors and evaluate their quality. Stem Cells 20:530–541

    PubMed  Google Scholar 

  • Serakinci N, Guldberg P, Burns JS, et al (2004) Adult human mesenchymal stem cell as a target for neoplastic transformation. Oncogene 23:5095–5098

    PubMed  CAS  Google Scholar 

  • Silva GV, Litovsky S, Assad JA, et al (2005) Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 111:150–156

    PubMed  CAS  Google Scholar 

  • Silzle T, Kreutz M, Dobler MA, Brockhoff G, Knuechel R, Kunz-Schughart LA (2003) Tumor-associated fibroblasts recruit blood monocytes into tumor tissue. Eur J Immunol 33:1311–1320

    PubMed  CAS  Google Scholar 

  • Silzle T, Randolph GJ, Kreutz M, Kunz-Schughart LA (2004) The fibroblast: sentinel cell and local immune modulator in tumor tissue. Int J Cancer 108:173–180

    PubMed  CAS  Google Scholar 

  • Sivridis E, Giatromanolaki A, Koukourakis MI (2005) Proliferating fibroblasts at the invading tumour edge of colorectal adenocarcinomas are associated with endogenous markers of hypoxia, acidity, and oxidative stress. J Clin Pathol 58:1033–1038

    PubMed  CAS  Google Scholar 

  • Sternlicht MD, Lochter A, Sympson CJ, et al (1999) The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell 98:137–146

    PubMed  CAS  Google Scholar 

  • Sternlicht MD, Bissell MJ, Werb Z (2000) The matrix metalloproteinase stromelysin-1 acts as a natural mammary tumor promoter. Oncogene 19:1102–1113

    PubMed  CAS  Google Scholar 

  • Studeny M, Marini FC, Champlin RE, Zompetta C, Fidler IJ, Andreeff M (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

    PubMed  CAS  Google Scholar 

  • Sugimoto T, Takiguchi Y, Kurosu K, et al (2005) Growth factor-mediated interaction between tumor cells and stromal fibroblasts in an experimental model of human small-cell lung cancer. Oncol Rep 14:823–830

    PubMed  CAS  Google Scholar 

  • Tlsty TD, Hein PW (2001) Know thy neighbor: stromal cells can contribute oncogenic signals. Curr Opin Genet Dev 11:54–59

    PubMed  CAS  Google Scholar 

  • Wiesen JF, Young P, Werb Z, Cunha GR (1999) Signaling through the stromal epidermal growth factor receptor is necessary for mammary ductal development. Development 126:335–344

    PubMed  CAS  Google Scholar 

  • Wright N, de Lera TL, Garcia-Moruja C, et al (2003) Transforming growth factor-beta1 down-regulates expression of chemokine stromal cell-derived factor-1: functional consequences in cell migration and adhesion. Blood 102:1978–1984

    PubMed  CAS  Google Scholar 

  • Xia Z, Ye H, Choong C, et al (2004) Macrophagic response to human mesenchymal stem cell and poly(epsilon-caprolactone) implantation in nonobese diabetic/severe combined immunodeficient mice. J Biomed Mater Res A 71:538–548

    PubMed  Google Scholar 

  • Yang F, Tuxhorn JA, Ressler SJ, McAlhany SJ, Dang TD, Rowley DR (2005) Stromal expression of connective tissue growth factor promotes angiogenesis and prostate cancer tumorigenesis. Cancer Res 65:8887–8895

    PubMed  CAS  Google Scholar 

  • Ye J, Yao K, Kim JC (2006) Mesenchymal stem cell transplantation in a rabbit corneal alkali burn model: engraftment and involvement in wound healing. Eye 20:482–490

    PubMed  CAS  Google Scholar 

  • Yoneda T, Hiraga T (2005) Crosstalk between cancer cells and bone microenvironment in bone metastasis. Biochem Biophys Res Commun 328:679–687

    PubMed  CAS  Google Scholar 

  • Zhu W, Xu W, Jiang R, et al (2006) Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol 80:267–274

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to F. Marini .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Hall, B., Andreeff, M., Marini, F. (2007). The Participation of Mesenchymal Stem Cells in Tumor Stroma Formation and Their Application as Targeted-Gene Delivery Vehicles. In: Kauser, K., Zeiher, AM. (eds) Bone Marrow-Derived Progenitors. Handbook of Experimental Pharmacology, vol 180. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-68976-8_12

Download citation

Publish with us

Policies and ethics