Interleukin 1 induces an autocrine loop hepatocyte growth factor/c-Met in murine Kaposi-like spindle cells.
Several cytokines, growth factors and the HIV transactivator Tat were shown to be involved in the pathogenesis of Kaposi's sarcoma. BKV/tat transgenic mice develop Kaposi's sarcoma-like lesions, and spindle-shaped cells (TTB) have been derived from these lesions. Here we show that TTB cells co-express hepatocyte growth factor (HGF) and its receptor, the product of the oncogene c-Met. An autocrine loop HGF/Met sustains spindle cell proliferation in vitro; indeed, an antisense oligomer targeted against HGF markedly inhibited cell growth. Moreover, HGF and Met are overexpressed after exposing TTB cells to the proinflammatory cytokine interleukin 1 (IL-1). We argue that upon exposure to IL-1, an HGF/Met autocrine loop is induced which could explain the appearance of multiple foci of uncontrolled growth. In addition, due to its angiogenic activity, HGF may also sustain the neovascularization typical of Kaposi's sarcoma lesions.
Maier
J
J
Department of Biomedical Sciences and Technologies-HSR, University of Milano, Italy.
Mariotti
M
M
Comoglio
P M
PM
Soria
M R
MR
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012514:Sarcoma, Kaposi / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D016376:Oligonucleotides, Antisense; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases