Abstract 1558: Imaging of metastatic B16F10 melanoma in mice using tumor-homing stem cells.

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Abstract Tumors, like wounds, recruit cells from surrounding tissues and bone marrow. Some of these cells provide support and nutrition, while others participate in an inflammatory response. Bone marrow mesenchymal stem cells (MSCs) exhibit this tropism toward wounds and other areas of pathology. Consequently, stem cell technology for diagnostic and therapeutic purposes is an emerging field in cancer biology. Like bone marrow MSCs, mouse neural progenitor cells (NPCs) tend to migrate toward cancer sites. We found that these cells migrate toward B16F10 lung melanomas, making them very good candidates for delivery of chemotherapeutic drugs, genes of interest, and imaging contrast agents. Among imaging techniques, bioluminescent imaging is non-invasive. Gaussia luciferase (Gluc) is particularly useful, as it is non-toxic and has stronger luminescence than other known luciferases. In the presence of its substrate coelenterazine (coel), Gluc luminescence peaks near 470 nm. In this study, we engineered NPCs to secrete Gluc. These Gluc-engineered cells were injected systemically to C57BL/6 mice bearing metastatic B16F10 lung melanoma and mice were given coel intravenously. Imaging of the mice on the Caliper IVIS Lumina II showed bioluminescence in disseminated areas. The distribution of bioluminescence suggested that the engineered NPCs migrated to the tumor sites and secreted Gluc. In confirmation, necropsy revealed black metastatic tumors in the locations emitting bioluminescence. Although IV injection of metastatic B16F10 lung melanoma cells usually generates lung tumors, we found dissemination of melanoma in other parts of the body. The Gluc-expressing NPCs could find the tumors as early as 2 days post tumor-cell injection, long before tumors were palpable. Thus, this system offers promise for improving cancer diagnosis. For improved imaging, this bioluminescence system can be coupled with other fluorescent dyes for red shifted output. Finally, the same sensitivity and tumor tropism suggests that the NPCs could be useful delivery cells for tumor-targeted therapeutics. Citation Format: Tej B. Shrestha, Sivasai Balivada, Matthew Basel, Marla Pyle, Stefan H. Bossmann, Deryl L. Troyer. Imaging of metastatic B16F10 melanoma in mice using tumor-homing stem cells. [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 1558. doi:10.1158/1538-7445.AM2013-1558