Abstract 2685: Regulation of melanoma metastasis by malignant melanoma-initiating cell marker ABCB5.

Abstract

Abstract Cancer stem cells drive tumor growth, including metastatic disease progression. ATP-binding cassette member B5 (ABCB5) expression identifies malignant melanoma initiating cells (MMICs), which are distinguishable from cancer bulk populations by their self-renewal and differentiation capacities, and pro-oncogenic interactions with the microenvironment. ABCB5 confers drug resistance in multiple human malignancies through its actions as a drug efflux transporter. Here, we demonstrate that ABCB5 also regulates melanoma metastasis. ABCB5 monoclonal antibody (mAb) treatment significantly inhibited metastasis development in highly immune-compromised NOD-scid IL2Rγnull mice carrying fully established human melanoma xenografts, independent of previously reported antibody-dependent cell-mediated cytotoxicity (ADCC) effects. ABCB5 mAb treatment was well tolerated, as indicated by equal body weights of treated mice and untreated controls. Moreover, ABCB5 mAb also inhibited melanoma cell invasive capacity, suggesting that ABCB5 regulates intravasation and/or extravasation of metastatic tumor cells. Furthermore, the average size of metastatic nodules in ABCB5 mAb-treated mice was significantly smaller than those in isotype control mAb-treated or untreated mice, indicating that ABCB5 also regulates proliferation of disseminated tumor cells. Expression profile analysis revealed that multiple known metastasis-associated genes are regulated by ABCB5. Rescue of their expression could reverse the anti-metastatic effects induced by ABCB5 inhibition. Thus, ABCB5 is not only a marker for MMICs, but functionally drives metastatic melanoma progression. Citation Format: Jie Ma, Allireza Alloo, Brian J. Wilson, Markus H. Frank. Regulation of melanoma metastasis by malignant melanoma-initiating cell marker ABCB5. [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 2685. doi:10.1158/1538-7445.AM2013-2685 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.