Abstract
Abstract Objectives. Tumor tissue produces abundant stromal cell-derived factor-1α (SDF-1α/CXCL12) that promotes recruitment of circulating stem/progenitor cells. We have recently found that SDF-1α induces elevated expression of CD162 and CD44, both are E-selectin ligands, on luminal endothelial cells lining capillaries. We thus postulate that highly expressed E-selectin ligands on tumor endothelium can serve as docking molecules to mediate specific homing of E-selectin-expressing circulating stem cells to tumor tissues. Here, we tested the role of E-selectin in mediating and facilitating homing of mesenchymal stem cells (MSC), which are modified to overexpress E-selectin, to SDF-1α−rich melanoma tissue. Methods. MSC from C57 BL6 and E-selectin-/- mice were enriched by culturing bone marrow cells in MesenCultTM medium. MSC were genetically labeled with luciferase (Luc2) or GFP in vitro. MSC from C57 BL6 mice were engineered to stably overexpress E-selectin (E-selectin+). Human melanoma cells were engineered to overexpress SDF-1α. 2 x 10^6 SDF-1α+/melanoma cells were pre-engrafted into NSG mice via tail-vein or subcu to form lung metastatic foci or skin melanoma, respectively. After 7-10 days, 1 x 10^6 E-selectin+ or E-selectin-/- MSC were injected into tumor-bearing mice through tail-vein or subcu, respectively. Homing of injected MSC to melanoma was assessed at various time points by IVIS (for Luc2+/MSC) and flow cytometry (for GFP+/MSC), respectively. Results. There were significantly increased numbers of engineered E-selectin-overexpressing MSC homing to melanoma tissues via systemic and local approaches, compared to control MSC or E-selectin-/-/MSC (p<0.05). Conclusions. E-selectin is an effective adhesion molecule in mediating tumor selective homing of MSC. Our study provides a useful method for targeted delivery of cells to tumor and may have therapeutic potential for developing stem cell-based cancer treatment. Citation Format: Cuixia Yang, Danjuan Li, Bo Wang, Omaida C. Velazquez, Zhao-Jun Liu. E-selectin mediates targeted delivery of mesenchymal stem cells to tumor. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 194. doi:10.1158/1538-7445.AM2014-194
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