Upregulation of thrombospondin-1 and angiogenesis in an aggressive human pancreatic cancer cell line selected for high metastasis
Year: 2009
Type: article
Abstract: Pancreatic cancer remains a leading cause of death despite its relatively low incidence. As in many other solid tumors, angiogenesis is critical to the growth and metastasis of this cancer. Through serial in vivo passages in mice, we have developed a highly aggressive variant of human pancreatic cancer cell line XPA-1 which shows more rapid primary tumor growth, faster time to metastasis, and more rapid lethality than the parental cell line. The high-metastatic variant developed a much denser tumor vasculature early during growth within the pancreas. Interestingly, examination of the in vitro growth of this aggressive variant yielded no significant difference from the parental cell line. Real-time PCR evaluation of genes involved in angiogenesis revealed a 24-fold increase in Thrombospondin-1 expression in cells derived from the high-metastatic variant when compared with the parental cell line. These findings provide direct evidence that elevated capability for angiogenesis, mediated by specific changes in gene expression, can lead to a large increase in cancer aggressiveness and resulting metastasis. These findings have important implications for the treatment of metastatic disease.
Source: Molecular Cancer Therapeutics
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: G2052325866, Dual-color tumor-host imaging models, Color-Coded Imaging of Pancreatic Cancer Microenvironment for Drug Discovery, G3578254857, Imageable Mouse Models of Pancreatic Cancer, G483852586, G518168165, Imageable Mouse Models of Pancreatic Cancer, Dual-color tumor-host imaging models, UCSD Cancer Center Training Program in Drug Development, Fluorophore-Conjugated Antibodies for Imaging and Resection of GI Tumors
OpenAlex ID: W2108200280