title: Growth factor PDGF-B/v-sis confers a tumorigenic phenotype to human tumor cells bearing PDGF receptors but not to cells devoid of receptors: evidence for an autocrine, but not a paracrine, mechanism.
abstract: Numerous established human tumor lines co-express platelet-derived growth factor (PDGF) and cognate receptors, suggesting that an autocrine and/or paracrine growth mechanism may be a causal or contributing mechanism to their transformed phenotype. Indeed, it is known that a PDGF-autocrine system is functional in several established tumor lines, especially in human gliomas, and a model for a functional paracrine mechanism has been established in a human melanoma line. However, at least 168 human cell lines representing 26 different human tumor types have been reported to continuously express PDGF-A and/or -B chains, and 55 of these also express PDGF receptors. For the majority of these cases, the significance of co-expression and the relative roles of autocrine and paracrine mechanisms in transformation remains unclear. Here, we show that human glioblastoma T98G cells co-express PDGF-B/c-sis and moderate levels of the cognate beta-type PDGF receptor (PR-beta) but are not tumorigenic in athymic mice. In contrast, human breast carcinoma MCF-7 cells do not express PR-beta and are tumorigenic. Clonal lines of each cell type with greatly increased secretion of p16w(T98Gsis and MCF-7sis cells) were characterized. T98Gsis cells are 85% tumorigenic and occasionally develop pulmonary metastases, showing that endogenous PR-beta can mediate complete transformation upon sufficient stimulation. In contrast, MCF-7sis cells exhibit some growth slowing in vitro and an exactly proportional decrease in tumor growth rate. We conclude that a PDGF-autocrine, and not a paracrine, mechanism best accounts for the acquired tumorigenicity of T98Gsis cells, thereby emphasizing the potential significance of expression of even moderate levels of PR-beta by human tumor cells.
authors.affiliation: The Sidney Kimmel Cancer Center, San Diego, CA, USA.
authors.forename: O
authors.initials: O
authors.lastname: Potapova
authors.forename: H
authors.initials: H
authors.lastname: Fakhrai
authors.forename: D
authors.initials: D
authors.lastname: Mercola
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000494:pharmacology; D000918:Antibody Specificity; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D005260:Female; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011233:Precipitin Tests; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000912:Antibodies, Neoplasm; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D017479:Receptors, Platelet-Derived Growth Factor