Abstract 5200: Effect of cancer-associated fibroblast on the progression of gastric cancer stem cells

Abstract

Abstract Introduction: Cancer stem cells (CSCs) are thought to possess the ability to initiate tumor growth and sustain self-renewal, which explains the tumorigenicity and the maintenance of bulk. There is an increasing evidence of the importance of the host microenvironment in conditioning the CSCs status, such as the stemness and the tumor initiation. Recently, cancer-associated fibroblasts in the cancer microenvironment have been suggested to be associated with the tumor progression. Then, the aim of this study is to clarify the relation between CSCs and cancer-associated fibroblasts. Material and Methods: A gastric cancer cell line, OCUM-12, and cancer-associated gastric fibroblasts, CaF-37, were used. Side population (SP) cells, known as CSCs rich population, were isolated from OCUM-12 cells by flowcytometry using Hoechst 33342, and were named as OCUM-12/SP. OCUM-12/SP cells or OCUM-12 cells were cultured with or without CaF-37 fibroblasts. The percentage of SP cells was evaluated by flowcytometry, and the growth of cancer cells was examined by cell number count. In vivo tumorigenicity of OCUM-12/SP cells was evaluated by subcutaneous inoculation in the presence or absence of CaF-37 fibroblasts. Results: The percentage of SP fraction of OCUM-12/SP cells was increased in the presence of CaF-37 fibroblasts. In contrast, CaF-37 fibroblasts significantly decreased the proliferation of OCUM-12/SP cells, while that of OCUM-12 cells was significantly increased by CaF-37 cells. The inoculation of 3×105, 1×105, and 3×104 OCUM-12/SP cells with 1×106 CaF-37 fibroblasts resulted in tumor formation in 5 (100%) of 5 mice, 4 (80%) of mice, 5 (100%) of 5 mice, respectively. However, the inoculation of 3×105, 1×105, and 3×104 OCUM-12/SP cells alone results in poor tumor formation at 3 (60%) of 5 mice, 0 (0%) of 5 mice, and 0 (0%) of 5 mice, respectively.Conclusion: Cancer-associated fibroblast might sustain the CSCs phenotype of stemness, and might increase the tumor initiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5200. doi:10.1158/1538-7445.AM2011-5200