Spindle cells isolated from Kaposi's sarcoma-like lesions of BKV/tat-transgenic mice co-express markers of different cell types.

Abstract

To characterize murine spindle cells isolated from Kaposi's sarcoma-like skin lesions developed in BK virus (BKV)/tat-transgenic mice. Kaposi's sarcoma-like spindle cells isolated from the lesions were propagated in vitro, and their phenotype was investigated using a panel of antibodies against various cell markers and angiogenic factors. Immunofluorescence and Western blot techniques were used. We observed co-expression of antigens specific for endothelial, smooth muscle and antigen-presenting cells, suggesting that cells from the TTB cell line represent poorly differentiated vascular precursors. Since TTB cells were derived from highly vascularized skin lesions, it is noteworthy that they synthesize a complex mixture of angiogenic factors, including fibroblast growth factor-2, vascular endothelial growth factor, placental growth factor, and hepatocyte growth factor. Due to their role in invasiveness and angiogenesis, we also observed the expression of urokinase plasminogen activator (uPA), uPA receptor, and plasminogen activator inhibitor-type 1 by TTB cells. Our results suggest that TTB cells share several features with human Kaposi's sarcoma spindle cells and can be a useful in vitro system to study the molecular mechanisms involved in Kaposi's sarcoma pathogenesis. Moreover, they synthesize a complex mixture of angiogenic factors and are growth-inhibited by the anti-angiogenic drug AGM-1470.