Over-expression of hepatocyte growth factor in human Kaposi's sarcoma

Autor: Jeanette A.M. Maier, Paola Comi, Massimo Mariotti, Maria Prat, Paolo M. Comoglio, Marco R. Soria, Adriana Albini
Rok vydání: 1996
Předmět:
Zdroj: International Journal of Cancer. 65:168-172
ISSN: 1097-0215
0020-7136
Popis: Kaposi’s sarcoma is a highly vascularired multifocal tumor which frequently appears as a complication of HIV infection. It has been suggested that a disorder in the cy-tokine network may contribute to the development of the disease. We examined the expression of several cytokines in human sporadic Kaposi’ssarcoma specimens, as well as in spindle cells cultured from human lesions, and consistently found high levels of expression of hepatocyte growth factor (HGF). In addition, human lesionderived spindle cells synthesize and secrete biologically active hepatocyte growth factor and express the hepatocyte-growthfactor receptor (c-MET). Moreover, elevated levels of transforming growth factor PI (TGFPI) mRNA were found in lesions of human sporadic Kaposi’s sarcoma and in lesion-derived spindle cells which also over-express urokinase. Since HGF, TGFP I and urokinase are all involved in capillary-vessel organization, dysregulation of these interacting agents may play a role in the initiation and/or progression of Kaposi’s sarcoma, stimulating the growth of spindle cells and recruiting endothelial cells into the lesion. o 1996 Wiley-Liss, Inc. Kaposi’s sarcoma (KS) in general, and acquired-immunodeficiency-syndrome-related KS (AIDS-KS) in particular, is an invasive and intensely angiogenic multifocal neoplasm of unknown cellular origin. It has been suggested that the multiple simultaneous KS lesions arise in response to systemic or micro-environmental alteration(s), such as increase in circulating cytokines, widespread dysregulation of the immune system, and/or multiple opportunistic infections. KS lesions contain a complex mixture of cell types, including fibroblasts, endothelial cells, dendritic cells and leukocytes of different lineages (Templeton, 1988). The presence of spindle cells is a distinctive histological marker of KS, and these cells are thought to be the proliferative component of the lesion. However, their nature and origin are highly controversial. The
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