Solid tumors are multicellular complexes where the tumor stroma that is comprised of endothelial cells, pericytes, fibroblasts and immune cells, all of which orchestrate to assist in cancer cell growth, angiogenesis and invasion. The tissue infiltration of immune cells is mediated by a multistep adhesion cascade and involves the selectin family of calcium-dependent cell surface glycoproteins Among this family, E-selectin (CD62E, ELAM-1 or LECAM-2) is exclusively expressed on the surface of endothelial cells in a highly inducible manner in response to inflammatory cytokines, and consequently an elevated E-selectin expression has been reported in many types of diseases including cancer. Endothelial E-selectin (eE-sel) assists in the initial adhesion of circulatory leukocytes to the surface of vascular endothelium by interacting with its ligands (sLeX, sLeA and CD44). The external domain of E-selectin can be cleaved off and shed into the circulation as soluble E-selectin (sE-sel). sE-sel is present in the serum of cancer patients and is associated with occurrence of metastases and poor survival in breast and colorectal cancers. However, the biological relevance of sE-sel is not clearly understood. In this study, we aim to identify the biological role of sE-sel in breast cancer growth. We have demonstrated that sE-sel enhances the adhesion and tissue migration of leukocytes into breast tumor both in vitro through the activation of PI3 kinase and its downstream signaling cascade. We have also demonstrated that 7 times more peripheral blood mononuclear cells (PBMC) migrate into breast tumor when pre-incubated with sE-sel as compared to untreated condition. Therefore, we conclude that sE-sel serves as a chemoattractant that enhances the tissue migration of leukocytes, which lead to the development of solid tumor stroma that enhances the growth of breast tumor and invasion.

Citation Format: Celine A. Blache, Nafis Hasan, Jeehna Park, Stephen Suh, David G. Gorenstein, Hallgeir Rui, Takemi Tanaka. A novel role of soluble E-selectin as a chemoatractant to human leukocytes through the PI3kinase signaling pathway in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4992. doi:10.1158/1538-7445.AM2013-4992

©2013 American Association for Cancer Research
2013