B49, a BST-2-based peptide, inhibits adhesion and growth of breast cancer cells

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.

Development and Characterization of the Shortest Anti-Adhesion Peptide Analogue of B49Mod1

“…We have previously shown that B49Mod1 is a BST-2-based peptide that inhibits cancer cell adhesion [32]. In this study, we show that a cysteine-linked disulfide bond is important for the antiadhesion activity of B49Mod1.…”

“…It has been previously shown that B49 and B49Mod1 possess anti-adhesion activity [32]. Since B49Mod1 contains cysteine residues that mediate BST-2 dimerization [12][13][14] and the adhesion-promoting function of BST-2 [29], we examined the role of cysteine-linked disulfide (S-S) bonds in the anti-adhesion function of B49Mod1.…”

“…In light of the oncogenic roles of BST-2 and its structural characteristics, we developed the first BST-2-based peptide series-B49/B49Mod1. The B49/B49Mod1 peptide series display potent inhibition of adhesion-dependent biological events in breast cancer cells [32,33]. The anti-adhesion B49/B49Mod1 peptides were designed based on the conserved sequence of the ECD of BST-2 [32].…”

“…The B49/B49Mod1 peptide series display potent inhibition of adhesion-dependent biological events in breast cancer cells [32,33]. The anti-adhesion B49/B49Mod1 peptides were designed based on the conserved sequence of the ECD of BST-2 [32]. In our previous study, the peptides were shown to block the interaction between breast cancer cells themselves, and between cancer cells and the ECM protein-fibronectin.…”

“…In our previous study, the peptides were shown to block the interaction between breast cancer cells themselves, and between cancer cells and the ECM protein-fibronectin. In addition, the peptide series inhibit cancer cell spheroid-formation, block the interaction of monocytes with cancer cells, and inhibit anchorage-independent growth, in addition to inhibiting tumor growth in the 4T1 mouse model of breast cancer [32]. However, the application of the B49/B49Mod1 peptide series is limited by its size.…”