Abstract 2856: Secretion modification region (SMR) peptide blocks migration and invasion in human breast cancer cells

Abstract

Abstract Background: Our group has discovered and developed a novel antagonist peptide, SMRwt. This peptide has dual roles as a tumor and HIV antagonist, through interaction with mortalin. It effectively suppresses breast cancer cell activity, growth, and release of EV [1], and inhibits release of HIV virus and EV during infection [2]. Aims: This study continued to explore the function and mechanism of interaction of the SMRwt peptide with mortalin during migration and invasion of breast cancer cells. It is known that changes in mortalin affect regulation of migration and invasive properties of human breast cancer epithelial cells, resulting in promoting metastatic potential. Methods: Breast cancer cells, either treated with SMRwt or SMRmut peptides, were assayed via the MTT assay, a cell wound-healing assay, and for migration, and invasion to determine the inhibitory role of these peptides on cell proliferation and migration/invasion. Flow cytometry and Western blot analysis were used to track expression of the peptides and mortalin and to measure expression of EV proteins. NanoSight analysis and acetylcholinesterase (AchE) assay were used for measuring EV size and concentration. Results: Our results demonstrate that the modified SMRwt peptides not only affected breast cancer cell proliferation and arrested breast cancer cell growth, but they also inhibited migration of breast cancer cells. In the wound-healing assay, an evident delay was observed in the wound closure of breast cancer cells treated for 24 h with SMRwt peptide while no delay was observed using the negative control peptide. Both SMRwt-CPP and PEG-SMRwt-CLU peptides decreased breast cancer cells migration ability in the tumor transendothelial migration assay. Proliferation of breast cancer cells was inhibited after a 24 h exposure to the SMRwt peptide as measured by MTT assay. Increased apoptosis rates were observed in tumor cells exposed to the SMRwt peptide and either paclitaxel or a mortalin inhibitor via flow cytometry. The above data indicate that SMRwt peptide/mortalin antagonism resulted in decreased capability for migration, invasion, and proliferation of tumor cells as well as increasing their capability to be killed via apoptosis. Conclusions: Breast cancer cells treated with SMRwt peptide displayed decreased ability of mortalin to do its function, which significantly affects tumor cell proliferation and reduces tumor cell invasion and migration. These results further support the role of mortalin in progression of breast cancer and support the role of the SMRwt peptide as an antagonist of mortalin function ultimately negatively modulating tumor metastasis. The peptide also antagonizes tumor EV release and reduces the expression of mortalin all of which could play a role in its effect on breast cancer cell invasion and metastasis suggesting the potential clinical applications of the peptide in late stage breast cancer chemotherapy. Citation Format: Ming Bo Huang, Jennifer Y. Wu, William W. Roth, James Lillard, Vincent C. Bond. Secretion modification region (SMR) peptide blocks migration and invasion in human breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2856.