Abstract 5905: Cancer associated fibroblasts promote tumor metastasis coexisting with cancer cells in blood circulation

Abstract

Abstract Background: Cancer associated fibroblasts (CAFs) are activated fibroblasts and an important player in the tumor microenvironment. Their activity promotes cancer cell proliferation, migration, and invasion, and metastasis. The most prognostic factor in tumor progression is metastasis. Cancer metastasis is a multi-step process that tumor cells detach from primary site, survive in the bloodstream, and seed in target organ. Although previous studies have focused on the interaction between CAFs and cancer cells in primary tumor site, the roles of CAFs in blood circulation remain largely unknown. We investigated the effect of CAFs coexisting with cancer cells in bloodstream on tumor metastasis in vivo mouse model, and also examined the effect of CAFs in subcutaneous tumor. Methods: We used female BALB/c-nu/nu mice and BALB/c mice in the experiments. Cancer cells were mouse mammary carcinoma cell lines 4T1 transfected with luciferase, colon cancer cell lines Colon 26 transfected with luciferase. Fibroblast cell lines were mouse embryonic fibroblast MEF and NIH-3T3. In venous injection mouse model, we injected 1 × 106 cancer cells alone or the same number of cancer and fibroblast co-cultured together. When we injected cancer cells transfected with luciferase, the mice were subjected to in vivo imaging system (IVIS) and measured luminescence intensity of metastatic sites. We have also harvested lung and compared its weight and metastatic nodule under microscopy. Furthermore, in subcutaneous tumor metastatic mouse model, cancer cells alone or mixed with cancer cells and CAFs were subcutaneously inoculated into the mice. Results: In the group of mice injected with cancer cells and fibroblasts, luminescent intensity of each lungs were higher than cancer cell alone. Harvested lung weight and the number of metastatic nodules were also higher in the group with cancer cells and fibroblasts.In subcutaneous model, mice inoculated with cancer cells and fibroblast had much more metastatic sites than cancer cells alone. Conclusions: Our data indicate that CAFs promote tumor metastasis by stimulating cancer cells in blood circulation, as well as in primary tumor site.These findings suggest that CAFs in both bloodstream and primary site could be a promising therapeutic target. CAF-targeted therapy could reduce tumor metastasis and improve the prognosis of cancer patients. Citation Format: Hajime Kashima, Kazuhiro Noma, Hiroaki Sato, Yuki Katsura, Takuya Kato, Toshiaki Ohara, Hiroshi Tazawa, Yasuhiro Shirakawa, Toshiyoshi Fujiwara. Cancer associated fibroblasts promote tumor metastasis coexisting with cancer cells in blood circulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5905. doi:10.1158/1538-7445.AM2017-5905