Down-regulation of the extracellular matrix protein SPARC in vSrc- and vJun-transformed chick embryo fibroblasts contributes to tumor formation in vivo.
In vitro transformation of primary cultures of chick embryo fibroblasts by the membrane-bound vSrc or the nuclear vJun oncoproteins is correlated with a down-regulation of the secreted glycoprotein SPARC (also called BM-40 or osteonectin). This protein is a nonstructural component of the extracellular matrix that is thought to regulate cell-matrix interaction during development, wound repair, and carcinogenesis. Its precise function remains unclear. To estimate the contribution of SPARC down-regulation to the major aspects of the transformed phenotype, we have reexpressed this protein from a self-replicating retrovirus Rcas, designated R-SPARC, in the transformed cultures. These R-SPARC-infected cultures display the following main properties: (i) they accumulate the SPARC protein to a level identical to or only slightly higher than the level in normal chick embryo fibroblasts; (ii) they retain the main phenotypic properties characteristic of in vitro transformed cells, that is, altered morphology, capacity to grow in a reduced amount of serum, and capacity to develop colonies from single cells in agar; (iii) they display a clearly reduced capacity to develop local fibrosarcomas in vivo. Taken together, these data strongly suggest that down-regulation of SPARC contributes to the transformed phenotype triggered by vSrc and vJun in primary avian fibroblasts, by facilitating in vivo tumorigenesis.
Vial
E
E
Unité de Virologie Humaine, Institut National de la Santé et de la Recherche Médicale (INSERM-U412), Ecole Normale Supérieure, Lyon, France.
Castellazzi
M
M
D000818:Animals; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002642:Chick Embryo; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D005354:Fibrosarcoma / Q000503:physiopathology*; D015870:Gene Expression; D016759:Oncogene Protein p65(gag-jun) / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015688:Oncogene Protein pp60(v-src) / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015676:Osteonectin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016326:Extracellular Matrix Proteins; D016759:Oncogene Protein p65(gag-jun); D015676:Osteonectin; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D015688:Oncogene Protein pp60(v-src)