Abstract 2649: Human adipose tissue-derived mesenchymal stem cells can target brain tumor initiating cells.

Abstract

Abstract Abstract The discovery of neural stem cells offers paradigm shift in brain tumor research. In neuro-oncology, the biology of neural stem cells has been pursued in two ways: as cancer stem cells to understand the origin and maintenance of brain tumors and as a potential cell-based vehicle for gene therapy. In addition to neural stem cells, mesenchymal stem cells (MSCs) have been reported to possess tumor-tropic migratory capacities. However, there is scanty data on migratory capacity of MSC toward brain tumor initiating cells (BTICs). This study focuses on investigating the ability of human adipose tissue derived MSCs (hAT-MSCs) to target BTICs and their cross-talk in the microenvironment. BTICs were isolated from three different kinds of brain tumors (medulloblastoma, atypical teratoid/rhabdoid tumor (ATRT), glioblastoma). The migration capacities of hAT-MSCs toward BTICs were examined both in vitro transwell assay and in vivo bioluminescence imaging analysis. To investigate the crosstalk between hAT-MSCs and BTICs, various cytokines were analyzed. Using co-culture system of hAT-MSCs and BTICs, we analyzed the mRNA expression patterns of cytokine receptors (CCR2, CCR4, CCR5, CCR7, CCR9, CCR10, XCR1, CXCR1, IL-8R, CXCR4, CX3CR1, IL1R1, IL6R, MET, PDGFRB, KDR, CD44, IFNAR1 and TEK) by qRT-PCR and protein level of their ligand in co-cultured media by Bio-Plex human cytokine ELISA. We confirmed the migratory capacity of t hAT-MSCs toward BTICs in vitro and BTICs-derived xenograft brain tumors in vivo live imaging. mRNA expression of receptors (CCR4, CCR5, CCR10, XCR1, CXCR1, IL-8R, CXCR4, PDGFRB, KDR, CD44, IFNAR1 and TEK) increased two- to eighteen-fold higher levels. The cytokine analysis revealed that the ligand levels of hAT-MSCs (medulloblastoma: VEGF, IL6, IL8, CCL3, CCL2 and TEK; ATRT: VEGF, CCL3 and TEK; glioblastoma: CCL2, PDGF, TEK and IGF1) and the ligand levels BTICs (medulloblastoma: CCL5 and CXCL4; ATRT: IL-8 and CXCL4; glioblastoma: CXCL4 and IGF1) were elevated in the co-cultured media. Our findings demonstrated that hAT-MSCs can target BTICs. Cross-talk between hAT-MSCs cytokine receptor and BTICs ligand (medulloblastoma: CCR5/CCL5 and CXCR4/CXCL4; ATRT: IL-8R/IL-8 and CXCR4/CXCL4; glioblastoma: CXCR4/CXCL4 and IGF1R/IGF1) play cardinal role in this process. Citation Format: Seung Ah Choi, Kyu-Chang Wang, Ji Hoon Phi, Ji Yeoun Lee, Jung Won Choi, Hyung Ah Kim, Se Hee Kim, Yong Hwy Kim, Sung Eun Kwon, Young-Hoon Kim, Seung-Ki Kim. Human adipose tissue-derived mesenchymal stem cells can target brain tumor initiating 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 2649. doi:10.1158/1538-7445.AM2013-2649