Extracellular matrix composition modulates angiosarcoma cell attachment and proliferation

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.

Genetic context of oncogenic drivers dictates vascular sarcoma development in aP2‐Cre mice

“…GSEA [32,33] indicated that the mouse angiosarcoma upregulated genes were also significantly enriched in human angiosarcomas (Figure 1C). Finally, gene ontology analysis of the 123 overlapping genes revealed terms related to cell cycle, extracellular matrix, and blood vessel development (Figure 1D and supplementary material, Table S4) consistent with recent findings in human and canine tumors emphasizing the role of extracellular matrix [12,38]. Furthermore, pathway analysis of genes enriched in the AKC cKO and AD cKO tumors revealed KEGG pathways such as RAP1 signaling, pathways in cancer, axon guidance, MAPK signaling, and focal adhesion (see supplementary material, Table S4).…”

Evaluation of the Mechanism of Jiedu Huazhuo Quyu Formula in Treating Wilson’s Disease-Associated Liver Fibrosis by Network Pharmacology Analysis and Molecular Dynamics Simulation

“…It has been reported that IL-6 and CXCL8 levels are related to the degree of liver fibrosis and can promote the process of liver fibrosis by inducing HSCs activation and regulating apoptosis [ 39 – 43 ]. It has also been shown that AKT regulates ECM degradation and that HSC activation aggravates liver fibrosis [ 44 ]. MAPK can induce liver inflammation and fibrosis, increase the extracellular matrix and affect the hypoxia inducible factor 1 subunit alpha (HIF-1 α ) signaling pathway to stimulate proliferation and activation of HSCs [ 45 – 49 ].…”