CHARACTERIZATION OF A MYOFIBROBLAST-LIKE CELL-LINE FROM AN ANGIOSARCOMA

We have isolated a cell line (ASMM) by serial passage of cells from ex plant cultures of an angiosarcoma resected from the calf of a 62 year old female. ASMM has been in continuous culture for over eighteen mont hs (>150 population doublings) and has a Fibroblast-like morphology wi th a doubling time of approximately 72 h. ASMM has a normal diploid ka ryology and is unable to generate tumors in nude mice or produce colon ies in soft agar. Examination of the cytoskeletal proteins shows both desmin and vimentin and a low level of alpha-smooth muscle actin, whic h can be upregulated by treatment with TGF beta. Low levels of basal V CAM-1 are significantly upregulated with TNF alpha and reduced by the presence of TCF beta. Basal ICAM-1 is also upregulated with TNF alpha and we show an additional upregulation through TGF beta. ASMM expresse s high levels of the hyaluronate receptor CD44, including the variant exons 6, 8 and 10. In addition, ASMM synthesises high levels of hyalur onate (HA), as did the original tumor. Unlike human umbilical vein end othelial cells (HUVECs) these cells were unable to generate capillary- like tubes when seeded onto basement membrane gels, and generated cord s of cells containing many synthetic organelles and intermediate filam ents. We were unable to detect the expression of factor VIII-related a ntigen, von Willebrand factor (vWF), CD31 or CD34, and were not able t o induce expression of E-selectin after TNF alpha stimulation. In conc lusion, this cell line represents a partially transformed population o f cells which show characteristics consistent with myofibroblast-like cells. The production of high levels of HA and expression of CD44 may help to explain the high degree of agressiveness of the tumor from whi ch ASMM was derived, as these molecules have been shown to play a role in cell motility and adhesion.