Environmental Factors Influencing Tumor Associated Pericyte Phenotype in Pancreatic Cancer

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the U.S. with a 5-year survival rate of 11%. PDAC patients suffer from the lack of effective treatment options largely due to the limited delivery efficacy of the drugs. Tumor vessels are abnormal, leaky, and lack proper pericyte coverage, contributing to elevated hypoxia and interstitial fluid pressure, promoting cancer progression and metastasis, and inhibiting drug delivery efficacy. In the case of PDAC, a large portion of blood vessels were covered by α-smooth muscle actin (αSMA) expressing pericyte, which is normally absent in capillary pericytes. We also showed that PDAC cancer cell-derived exosomes could induce αSMA expression in the pericyte suggesting the pericyte phenotype is influenced by the Tumor Microenvironment (TME). Induced αSMA expression in pericyte disrupted the 3D tube formation efficiency when cultured with endothelial cells suggesting αSMAhigh pericyte confers a pathological feature of tumor blood vessels.