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Amatangelo MD , Bassi DE , Klein-Szanto AJP , Cukierman E
Stroma-derived three-dimensional matrices are necessary and sufficient to promote desmoplastic differentiation of normal fibroblasts
American Journal of Pathology. 2005 ;167(2) :475-488
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Abstract
Stromagenesis is a host reaction of connective tissue that, when induced to cancer, produces a progressive and permissive mesenchymal microenvironment, thereby supporting tumor progression. The stromal microenvironment is complex and comprises several cell types, including fibroblasts, the primary producers of the noncellular scaffolds known as extracellular matrices. The events that support tumor progression during stromagenesis are for the most part unknown due to the lack of suitable, physiologically relevant, experimental model systems. In this report, we introduce a novel in vivo-like three-dimensional system derived from tumor-associated fibroblasts at diverse stages of tumor development that mimic the stromagenic features of fibroblasts and their matrices observed in vivo. Harvested primary stromal fibroblasts, obtained from different stages of tumor development, did not retain in vivo stromagenic characteristics when cultured on traditional two-dimensional substrates. However, they were capable of effectively maintaining the tumor-associated stromal characteristics within three-dimensional cultures. In this study, we demonstrate that in vivo-like three-dimensional matrices appear to have the necessary topographical and molecular information sufficient to induce desmoplastic stroma differentiation of normal fibroblasts. Copyright © American Society for Investigative Pathology.
Notes
00029440 (ISSN) Cited By: 2; Export Date: 25 May 2006; Source: Scopus CODEN: AJPAA Language of Original Document: English Correspondence Address: Cukierman, E.; Basic Science/Tumor Cell Biology; Fox Chase Cancer Center; 333 Cottman Ave. Philadelphia, PA 19111-2497, United States; email: edna.cukierman@fccc.edu Chemicals/CAS: 7,12 dimethylbenz[a]anthracene, 57-97-6, 9,10-Dimethyl-1,2-benzanthracene, 57-97-6 References: Bissell, M.J., Radisky, D., Putting tumours in context (2001) Nat Rev Cancer, 1, pp. 46-54; Kunz-Schughart, L.A., Knuechel, R., Tumor-associated fibroblasts (part I): Active stromal participants in tumor development and progression? (2002) Histol Histopathol, 17, pp. 599-621; Kunz-Schughart, L.A., Knuechel, R., Tumor-associated fibroblasts (part II): Functional impact on tumor tissue (2002) Histol Histopathol, 17, pp. 623-637; Silzle, T., Randolph, G.J., Kreutz, M., Kunz-Schughart, L.A., The fibroblast: Sentinel cell and local immune modulator in tumor tissue (2004) Int J Cancer, 108, pp. 173-180; Mueller, M.M., Fusenig, N.E., Friends or foes-bipolar effects of the tumour stroma in cancer (2004) Nat Rev Cancer, 4, pp. 839-849; Li, G., Satyamoorthy, K., Meier, F., Berking, C., Bogenrieder, T., Herlyn, M., Function and regulation of melanoma-stromal fibroblast interactions: When seeds meet soil (2003) Oncogene, 22, pp. 3162-3167; Mueller, M.M., Fusenig, N.E., Tumor-stroma interactions directing phenotype and progression of epithelial skin tumor cells (2002) Differentiation, 70, pp. 486-497; Beacham, D.A., Cukierman, E., Stromagenesis: The changing face of fibroblastic microenvironments during tumor progression Semin Cancer Biol, in press; Cukierman, E., A visual-quantitative analysis of fibroblastic stromagenesis in breast cancer progression (2004) J Mammary Gland Biol Neoplasia, 9, pp. 311-324; Bauer, G., Elimination of transformed cells by normal cells: A novel concept for the control of carcinogenesis (1996) Histol Histopathol, 11, pp. 237-255; Kuperwasser, C., Chavarria, T., Wu, M., Magrane, G., Gray, J.W., Carey, L., Richardson, A., Weinberg, R.A., Reconstruction of functionally normal and malignant human breast tissues in mice (2004) Proc Natl Acad Sci USA, 101, pp. 4966-4971; Maffini, M.V., Soto, A.M., Calabro, J.M., Ucci, A.A., Sonnenschein, C., The stroma as a crucial target in rat mammary gland carcinogenesis (2004) J Cell Sci, 117, pp. 1495-1502; Abelev, G.I., Differentiation antigens: Dependence on carcinogenesis mechanisms and tumor progression (a hypothesis) (2003) Mol Biol, 37, pp. 2-8; Park, C.C., Bissell, M.J., Barcellos-Hoff, M.H., The influence of the microenvironment on the malignant phenotype (2000) Mol Med Today, 6, pp. 324-329; Elenbaas, B., Weinberg, R.A., Heterotypic signaling between epithelial tumor cells and fibroblasts in carcinoma formation (2001) Exp Cell Res, 264, pp. 169-184; Mareel, M., Leroy, A., Clinical, cellular, and molecular aspects of cancer invasion (2003) Physiol Rev, 83, pp. 337-376; Olumi, A.F., Grossfeld, G.D., Hayward, S.W., Carroli, P.R., Tlsty, T.D., Cunha, G.R., Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium (1999) Cancer Res, 59, pp. 5002-5011; Quaranta, V., Giannelli, G., Cancer invasion: Watch your neighbourhood! (2003) Tumori, 89, pp. 343-348; Sung, S.Y., Chung, L.W., Prostate tumor-stroma interaction: Molecular mechanisms and opportunities for therapeutic targeting (2002) Differentiation, 70, pp. 506-521; Nakagawa, H., Liyanarachchi, S., Davuluri, R.V., Auer, H., Martin Jr., E.W., De La Chapelle, A., Frankel, W.L., Role of cancer-associated stromal fibroblasts in metastatic colon cancer to the liver and their expression profiles (2004) Oncogene, 23, pp. 7366-7377; Noel, A., Kebers, F., Maquol, E., Foidart, J.M., Cell-cell and cell-matrix interactions during breast cancer progression (1999) Curr Top Pathol, 93, pp. 183-193; Tuxhorn, J.A., Ayala, G.E., Rowley, D.R., Reactive stroma in prostate cancer progression (2001) J Urol, 166, pp. 2472-2483; Desmouliere, A., Guyot, C., Gabbiani, G., The stroma reaction myofibroblast: A key player in the control of tumor cell behavior (2004) Int J Dev Biol, 48, pp. 509-517; Dugina, V., Alexandrova, A., Chaponnier, C., Vasiliev, J., Gabbiani, G., Rat fibroblasts cultured from various organs exhibit differences in alpha-smooth muscle actin expression, cytoskeletal pattern, and adhesive structure organization (1998) Exp Cell Res, 238, pp. 481-490; Gabbiani, G., The myofibroblast in wound healing and fibrocontractive diseases (2003) J Pathol, 200, pp. 500-503; Schor, S.L., Ellis, I.R., Jones, S.J., Baillie, R., Seneviratne, K., Clausen, J., Motegi, K., (...), Kay, R.A., Migration-stimulating factor: A genetically truncated onco-fetal fibronectin isoform expressed by carcinoma and tumor-associated stromal cells (2003) Cancer Res, 63, pp. 8827-8836; Bondeson, L., Lindholm, K., Prediction of invasiveness by aspiration cytology applied to nonpalpable breast carcinoma and tested in 300 cases (1997) Diagn Cytopathol, 17, pp. 315-320; Han, S., Sidell, N., Roser-Page, S., Roman, J., Fibronectin stimulates human lung carcinoma cell growth by inducing cyclooxygenase-2 (COX-2) expression (2004) Int J Cancer, 111, pp. 322-331; Liotta, L.A., Kohn, E.C., The microenvironment of the tumour-host interface (2001) Nature, 411, pp. 375-379; Cukierman, E., Cell migration analyses within fibroblast-derived 3-D matrices (2004) Cell Migration: Developmental Methods and Protocols, pp. 79-93, Edited by Guan J. Totowa, Humana Press; Cukierman, E., Preparation of extracellular matrices produced by cultured fibroblasts (2002) Current Protocols in Cell Biology, pp. 10.19.11-10.19.14, Edited by Bonifacino JS, Dasso M, Lippincott-Schwartz J, Harford JB, Yamada KM. Philadelphia, John K. Wiley & Sons; Cukierman, E., Pankov, R., Stevens, D.R., Yamada, K.M., Taking cell-matrix adhesions to the third dimension (2001) Science, 294, pp. 1708-1712; DiGiovanni, J., Multistage carcinogenesis in mouse skin (1992) Pharmacol Ther, 54, pp. 63-128; Quade, B.J., McDonald, J.A., Fibronectin's amino-terminal matrix assembly site is located within the 29-kDa amino-terminal domain containing five type I repeats (1988) J Biol Chem, 263, pp. 19602-19609; Labat-Robert, J., Fibronectin in malignancy: Effect of aging (2002) Semin Cancer Biol, 12, pp. 187-195; Velling, T., Risteli, J., Wennerberg, K., Mosher, D.F., Johansson, S., Polymerization of type I and III collagens is dependent on fibronectin and enhanced by integrins a11b1 and a2b 1 (2002) J Biol Chem, 277, pp. 37377-37381; Sottile, J., Hocking, D.C., Fibronectin polymerization regulates the composition and stability of extracellular matrix fibrils and cell-matrix adhesions (2002) Mol Biol Cell, 13, pp. 3546-3559; McDonald, J.A., Kelley, D.G., Broekelmann, T.J., Role of fibronectin in collagen deposition: Fab' to the gelatin-binding domain of fibronectin inhibits both fibronectin and collagen organization in fibroblast extracellular matrix (1982) J Cell Biol, 92, pp. 485-492; Pupa, S.M., Menard, S., Forti, S., Tagliabue, E., New insights into the role of extracellular matrix during tumor onset and progression (2002) J Cell Physiol, 192, pp. 259-267; Hsu, M.Y., Meier, F., Herlyn, M., Melanoma development and progression: A conspiracy between tumor and host (2002) Differentiation, 70, pp. 522-536; Ruiter, D., Bogenrieder, T., Elder, D., Herlyn, M., Melanoma-stroma interactions: Structural and functional aspects (2002) Lancet Oncol, 3, pp. 35-43; Buttery, R.C., Rintoul, R.C., Sethi, T., Small cell lung cancer: The importance of the extracellular matrix (2004) Int J Biochem Cell Biol, 36, pp. 1154-1160; Balaban, N.Q., Schwarz, U.S., Rivellne, D., Goichberg, P., Tzur, G., Sabanay, I., Mahalu, D., (...), Gelger, B., Force and focal adhesion assembly: A close relationship studied using elastic micropatterned substrates (2001) Nat Cell Biol, 3, pp. 466-472; Geiger, B., Bershadsky, A., Assembly and mechanosensory function of focal contacts (2001) Curr Opin Cell Biol, 13, pp. 584-592; Geiger, B., Bershadsky, A., Pankov, R., Yamada, K.M., Transmembrane crosstalk between the extracellular matrix and the cytoskeleton (2001) Nat Rev Mol Cell Biol, 2, pp. 793-805; Yamada, K.M., Pankov, R., Cukierman, E., Dimensions and dynamics in integrin function (2003) Braz J Med Biol Res, 36, pp. 959-966; Cukierman, E., Pankov, R., Yamada, K.M., Cell interactions with three-dimensional matrices (2002) Curr Opin Cell Biol, 14, pp. 633-640; Geiger, B., Cell biology: Encounters in space (2001) Science, 294, pp. 1661-1663; Xia, H., Nho, R.S., Kahm, J., Kleidon, J., Henke, C.A., Focal adhesion kinase is upstream of phosphatidylinositol 3-kinase/Akt in regulating fibroblast survival in response to contraction of type I collagen matrices via a beta 1 integrin viability signaling pathway (2004) J Biol Chem, 279, pp. 33024-33034; Walpita, D., Hay, E., Studying actin-dependent processes in tissue culture (2002) Nat Rev Mol Cell Biol, 3, pp. 137-141; Wozniak, M.A., Modzelewska, K., Kwong, L., Keely, P.J., Focal adhesion regulation of cell behavior (2004) Biochim Biophys Acta, 1692, pp. 103-119; Cheng, J.D., Weiner, L.M., Tumors and their microenvironments: Tilling the soil Clin Cancer Res, 9, pp. 1590-1647, 2203; Pikarsky, E., Porat, R.M., Stein, I., Abramovitch, R., Amit, S., Kasem, S., Gutkovich-Pyest, E., (...), Ben-Neriah, Y., NF-[kappa]B functions as a tumour promoter in inflammation-associated cancer (2004) Nature, 431, pp. 461-466; Eikmans, M., Baelde, J.J., De Heer, E., Bruijn, J.A., ECM homeostasis in renal diseases: A genomic approach (2003) J Pathol, 200, pp. 526-536; Van Kempen, L.C., Ruiter, D.J., Van Muijen, G.N., Coussens, L.M., The tumor microenvironment: A critical determinant of neoplastic evolution (2003) Eur J Cell Biol, 82, pp. 539-548; Hinz, B., Gabbiani, G., Chaponnier, C., The NH2-terminal peptide of alpha-smooth muscle actin inhibits force generation by the myofibroblast in vitro and in vivo (2002) J Cell Biol, 157, pp. 657-663; Stephens, P., Grenard, P., Aeschlimann, P., Langley, M., Blain, E., Errington, R., Kipling, D., (...), Aeschlimann, D., Crosslinking and G-protein functions of transglutaminase 2 contribute differentially to fibroblast wound healing responses (2004) J Cell Sci, 117, pp. 3389-3403; Verderio, E.A., Johnson, T., Griffin, M., Tissue transglutaminase in normal and abnormal wound healing (2004) Amino Acids, 26, pp. 387-404; He, Y.L., Macarak, E.J., Korostoff, J.M., Howard, P.S., Compression and tension: Differential effects on matrix accumulation by periodontal ligament fibroblasts in vitro (2004) Connect Tissue Res, 45, pp. 28-39.