Abstract 2435: Chromogranin A and its N-terminal fragment affect the metastatic potential of circulating tumor cells in mice

Abstract

Abstract Chromogranin A (CgA) is an acidic glycoprotein present within secretory vesicles of many normal and neoplastic endocrine and neuroendocrine cells. CgA is abnormally released in circulation in patients with neuroendocrine tumors and non neuroendocrine tumors, as in a subpopulation of patients with non small cell lung cancer (NSCLC), with important prognostic implications. We have previously demonstrated that CgA can preserve the barrier function of the vascular endothelium. Since hematogenous metastasis requires the seeding of malignant cancer cells in circulation, followed by cell extravasation and colonization of distant organs, we investigated the role of CgA on tumor cell extravasation and lung colony formation. We show that normal levels of endogenous CgA can reduce the number of lung colonies from mammary TS/A adenocarcinoma cells injected into the venous circulation of mice. Administration of omeprazole, a drug commonly used in the treatment of acid-peptic disorders, increased the blood levels of CgA and further inhibited the development of lung colonies in a CgA-dependent manner. Furthermore, administration of recombinant CgA or its N-terminal fragment (called vasostatin-1, VS-1) reduced the metastatic potential of circulating mammary TS/A adenocarcinoma and B16-F10 melanoma cells. Studies on the mechanism of action showed that CgA and VS-1 can inhibit the transendothelial migration of cancer cells, by preserving the VE-cadherin-dependent endothelial barrier function. These findings suggest that endogenous CgA can play a role as a modulator of the metastatic potential of circulating tumor cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2435. doi:10.1158/1538-7445.AM2011-2435