Abstract 1414: Regulation of tumor cell trafficking by chromogranin A

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 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. This prompted us to investigate the role of circulating CgA on metastasis development and tumor self-seeding, the ability of tumor cells to re-infiltrate their tumor of origin. Using mouse mammary adenocarcinoma models we observed that CgA inhibits both tumor self-seeding and organ colonization. Studies of the mechanism of action showed that CgA can inhibit the shedding of cancer cells in circulation from primary tumors, the re-infiltration of tumors and the colonization of lungs by circulating tumor cells. Pharmacological modulation of CgA further affected the development of lung colonies by tumor cells. We obtained evidences to suggest that CgA can inhibit the transendothelial migration of cancer cells, by preserving the VE-cadherin-dependent endothelial barrier function. These findings point to a role of circulating CgA as a regulator of tumor cell trafficking from tumor-to-blood and from blood-to-tumor/normal tissues. Inhibition of the multidirectional trafficking of cancer cells in normal and neoplastic tissues may represent a novel strategy to reduce cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1414. doi:1538-7445.AM2012-1414