Modeling human endothelial cell transformation in vascular neoplasias

Abstract

Endothelial cell (EC)-derived neoplasias range from benign hemangioma to aggressive metastatic angiosarcoma, which responds poorly to current treatments and has a very high mortality rate. The development of treatments that are more effective for these disorders will be expedited by insight into the processes that promote abnormal proliferation and malignant transformation of human ECs. The study of primary endothelial malignancy has been limited by the rarity of the disease; however, there is potential for carefully characterized EC lines and animal models to play a central role in the discovery, development and testing of molecular targeted therapies for vascular neoplasias. This review describes molecular alterations that have been identified in EC-derived neoplasias, as well as the processes that underpin the immortalization and tumorigenic conversion of ECs. Human EC lines, established through the introduction of defined genetic elements or by culture of primary tumor tissue, are catalogued and discussed in relation to their relevance as models of vascular neoplasia.

Well-differentiated angiosarcoma of spleen: a teaching case mimicking hemagioma and cytogenetic analysis with array comparative genomic hybridization

“…The result in this case was the same as reported elsewhere that angiosarcoma often displayed complex chromosome aberration [ 13 ]. The previous researches that benign vascular neoplasm often shows simple chromosome abnormality may support the malignant nature of the present case [ 21 ]. Notably, this observation raises possibility that even well-differential angiosarcoma may presents complex chromosome abnormality.…”

Effective Management of Advanced Angiosarcoma by the Synergistic Combination of Propranolol and Vinblastine-based Metronomic Chemotherapy: A Bench to Bedside Study

“…Immortalized and transformed endothelial cells were developed to better understand vascular tumors, such as angiosarcoma, and to evaluate the therapeutic potential of conventional and novel drugs against these malignancies ( Wen and MacKenzie, 2013 ). Although immortalized murine endothelial cells have been shown to form benign hemangiomas in vivo , the introduction of oncogenic HRAS produced rapidly growing and poorly differentiated angiosarcomas ( Cao et al, 2010 ).…”

Development of Immortalized Human Tumor Endothelial Cells from Renal Cancer

“…Therefore, the ectopic expression of the hTERT gene has also been used as an alternative method for immortalization. However, the induction of hTERT alone is sometimes not enough [33]. Indeed, when we transducted hTERT alone in ECs, their life span was prolonged but not immortalized (data not shown).…”