Abstract
Bone marrow stromal antigen 2 (BST-2) also known as Tetherin has been implicated in the growth and progression of many cancers. BST-2 employs its pro-tumor effects through the formation of BST-2:BST-2 dimers which ultimately promotes cell to cell and cell to matrix adhesion, cell motility, survival, and growth. The aim of this study was to evaluate the effect of a novel BST-2-based peptide-B49 on adhesion and growth of breast cancer cells. Homotypic/heterotypic adhesion, three-dimensional spheroid formation, and anchorage-independent growth were used to assess the effect of B49 on cell adhesion and growth. Additionally, we provide evidence of the anti-tumor effect of B49 in a preclinical mouse model of breast cancer. Results show that breast cancer cell adhesion to other cancer cells or components of the tumor microenvironment were inhibited by B49. Most well-known evaluation indexes of cancer cell growth, including spheroid formation, anchorage-independent, and primary tumor growth were significantly inhibited by B49. These data affirm that i) BST-2 plays a key role in mediating breast cancer cell adhesion and growth, and ii) B49 and its analog B49Mod1 significantly inhibits BST-2-mediated cancer cell adhesion and growth. Therefore, B49 and its analogs offer a promising anti-adhesion and therapeutic lead for BST-2-dependent cancers.