Exogenous fibroblast growth factor-2 induces a transformed phenotype in vascular kaposi's sarcoma-like cells.
Vascular TTB cells derive from murine Kaposi's sarcoma-like dermal lesions and share several phenotypic features with AIDS-associated KS spindle cells. We have recently reported that fibroblast growth factor-2 (FGF-2) promotes dramatic cytoskeletal and morphological alterations in TTB cells, concomitant with the induction of an autocrine loop for hepatocyte growth factor and a relocalization of the urokinase receptor. Since all these alterations are hallmarks of cell transformation. we attempted to verify whether FGF-2 induces a transformed phenotype in TTB cells. Our results show that FGF-2-treated TTB cells acquire the ability to grow under anchorage-independent conditions. In addition, FGF-2 markedly reduced the levels of thrombospondin-1, an antiangiogenic and tumor suppressor protein, in TTB cells. Therefore, FGF-2 induces KS-like spindle cells to acquire properties characteristic of transformed cells. This suggests that FGF-2 plays a pathogenetic role in KS not only by promoting angiogenesis, but also by conferring a transformed phenotype upon KS cells. In light of previous reports on Tat-induced release of FGF-2 into the extracellular space, our findings may provide an additional mechanism for the observed synergism between Tat and FGF-2 in the pathogenesis of KS.
Cavallaro
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Dibit, Scientific Institute San Raffaele, Milan, Italy. cavallaro@nt.imp.univie.ac.at
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D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D015696:Gene Products, tat / Q000235:genetics; D006678:HIV / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D012514:Sarcoma, Kaposi / Q000378:metabolism* / Q000473:pathology; D012685:Sepharose / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D019700:Thrombospondin 1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D019700:Thrombospondin 1; D054322:tat Gene Products, Human Immunodeficiency Virus; D016222:Fibroblast Growth Factor 2; D012685:Sepharose