Abstract A23: The crosstalk between developmental endothelial locus 1 (DEL-1) and cancer stem cells in murine melanoma: A potential modality of local control

Abstract

Abstract Introduction: Developmental endothelial locus-1 is a homeostatic factor in the central nervous system limiting neuroinflammation and demyelination. Del-1 has an endothelial cell–restricted pattern, particularly in the embryo. However, our data now for the first time provide evidence that melanoma cells express Del-1. The relatively newly described cancer stem cells (CSCs) are tumor-initiating cells (TICs) that often survive therapy and give rise to second-line tumors by self-renewal and differentiation into multiple cell types. CSCs are proposed to persist in tumors as a distinct population and to cause relapse and metastasis by giving rise to new tumors. Therefore, development of specific therapies targeted at CSCs holds hope for improvement of survival and quality of life of cancer patients, especially those with metastatic disease. Methods: C57/BL6 mice were injected with B16F10 murine melanoma cell line (1 x 106 cells/mouse, subcutaneous). Tumor growth monitored. Controls (Group 2) received vehicle only (PBS). Once the first tumor reached 12mm in size, the mice were sacrificed and tumor cells subjected to flow-cytometry, and statistical analysis, and p-values <0.05 considered significant. our novel findings suggest a regulatory role for Del-1 in cancer. Alteration of inflammatory indices, apoptosis, and necroptosis with ultimate affects on tumor size and growth were all may be potentially regulated partially by a Del-1 dependent mechanism. Results: Our data showed for the first time that DEL-1 was expressed by CSCs as well as typic non stem cells tumor cells in a murine melanoma model. These DEL-1-expressing CSCs may be palying a role in tumor angiogenesis. Further, DEL-1 is capable of suppressing T lymphocyte infiltration into the tumor microenvironment. our novel findings suggest a regulatory role for Del-1 in cancer. Alteration of inflammatory indices, apoptosis, and necroptosis with ultimate affects on tumor size and growth (by affecting Cancer Stem Cells) were all may be potentially regulated partially by a Del-1 dependent mechanism. Conclusion: Our data propose a novel hypothesis that development of tumor and CSCs activity may be affected by angiogenic and regulatory nature of Del-1. Furthermore, our results suggest a therapeutic role for Del-1 as a novel modality in cancer treatment. Citation Format: James Walker, marsha kocherla, Blake christianson, Xu qin, Jack C. yu, Babak baban. The crosstalk between developmental endothelial locus 1 (DEL-1) and cancer stem cells in murine melanoma: A potential modality of local control. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr A23.