Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
AUTOCRINE AND PARACRINE MECHANISMS IN THE EVOLUTION OF KAPOSI'S SARCOMA
Int Congress Ser; (925):277-80 1990. Unique Identifier : AIDSLINE ICDB/92679907 Biberfeld P; Nakamura S; Ensoli B; Salahuddin ZS; Barillari G; Parravicini C; Gendelman R; Kaaya E; Gallo RC; Immunopathology Lab., Dept. of Pathology, Karolinska Inst.,; Stockholm, Sweden
Abstract:
Culture conditions were developed recently that permit the continuous in vitro propagation of Kaposi's sarcoma (KS)-derived cells, thus permitting their genomic, phenotypic, and functional characterization. Various phenotypic features appeared most likely to correspond to the characteristic spindle cells usually thought to represent the tumor cells of the KS lesions. Cells were transplanted to nude mice under various conditions. No lasting local growth or tissue spreading of the KS cells was observed, but a conspicuous host (mouse) angiogenic response was seen consistently around the site of the KS cell deposit, provided viable cells were inoculated. Use of the chorioallantoic membrane assay consistently indicated the release by KS cells of a potent angiogenic factor(s) compared to fixed cells or to various cultured control cell preparations. KS-derived cells expressed fibroblast growth factor, interleukin-1, transforming growth factor beta, granulocyte-macrophage colony-stimulating factor, and platelet-derived growth factor beta. Supernatants of cultured KS-derived cells could stimulate the growth of endothelial cells (paracrine stimulation) as well as of KS cells themselves (autocrine stimulation). A pathogenic model for the evolution of the KS lesion has been proposed based on the in vivo autocrine and paracrine effects of these cytokines. Although the model needs to be validated, the local triggering and perpetuation of such a specific cytokine cascade by the spindle cells of the KS lesions could provide a common denominator in the pathogenesis of the various forms of KS. The pathogenic mechanism(s) responsible for the initial triggering of the spindle cells is not clear, but initial observations indicate that a factor(s) produced by retrovirus-activated T cells can selectively stimulate the outgrowth of spindle cells, which may develop pleiotropic, paracrine, and autocrine effects in the tissues. Recently, a regulatory gene product (tat) of HIV has been shown to stimulate KS cell growth in vitro, in keeping with observations of the development of KS-like lesions in tat transgenic mice. (13 Refs)
Keywords: Angiogenesis Factor/*METABOLISM Animal Fibroblast Growth Factor/METABOLISM Gene Expression Gene Products, tat/METABOLISM Granulocyte-Macrophage Colony-Stimulating Factor/*METABOLISM Human HTLV-BLV Viruses/METABOLISM Interleukin-1/*METABOLISM Mice Mice, Nude Platelet-Derived Growth Factor/*METABOLISM Sarcoma, Kaposi's/GENETICS/*METABOLISM Transforming Growth Factors/*METABOLISM MEETING PAPER
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Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
