Abstract
Angiosarcoma is a rare and generally fatal tumor composed of aberrant cells of endothelial origin. Because of its infrequency in humans, very little is known about the growth requirements of this vascular sarcoma. Unlike the rapidly proliferating solid tumors from which they are isolated from, many of the established angiosarcoma cell lines exhibit less than robust growth in culture and often fail to form tumors in xenograft models. In order to better understand angiosarcoma in vitro growth conditions, we focused on a singular aspect of their culture—adhesion to the extracellular matrix—in order to identify attachment substrates that may facilitate and/or enhance their growth in tissue culture. Our data indicates that the extracellular matrix of angiosarcomas contains similar protein compositions to that of non-diseased endothelial cells. Moreover, angiosarcoma cell lines exhibited strong attachment preference to substrates such as collagen I or fibronectin, and less preference to collagen IV, laminin, or tropoelastin. Growth on preferred extracellular matrix substrates promoted mitogenic signaling and increased proliferation of angiosarcoma cell lines. These findings provide insight that may lead to more successful in vitro growth of angiosarcoma cell lines.
Highlights
Angiosarcoma is a rare and clinically highly variable malignant neoplasm composed of rapidly dividing, aggressively infiltrating cells of endothelial origin
We compared the expression of angiosarcoma extracellular matrix (ECM) proteins and their regulators to those found in nondiseased endothelium, observing positive antigenicity for fibronectin, collagen I, collagen IV, collagen V, collagen VI, MMP1, MMP2, and MMP13 in 6 angiosarcoma tumors and 10 non-diseased vascular tissues (Figure 1A)
Given the influence of ECM composition on sustained intracellular signaling changes in angiosarcoma cells, we evaluated the effect of fibronectin verses collagen IV on cell proliferation using our panel of angiosarcoma cell lines and non-diseased endothelial cell controls
Summary
Angiosarcoma is a rare and clinically highly variable malignant neoplasm composed of rapidly dividing, aggressively infiltrating cells of endothelial origin. The mortality rate of patients with angiosarcoma is exceptionally high as this tumor type responds very poorly to traditional treatment therapies, with a median survival time of between 3 to 8 months depending on TNM staging and location of the tumor [1, 2]. Purification of angiosarcoma cells from solid tumors remains a challenge, and once isolated many of these cells lines exhibit unexpectedly slow proliferation rates that are not at all reflective of their rapid and lethal dissemination in patients with the disease, and generally fail to recapitulate aggressive solid tumors in xenograft models. Methodologies that could facilitate the isolation and maintenance of angiosarcoma cell lines could greatly improve opportunities to discover effective treatments against this rare disease
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