Abstract 2742: Bone marrow-derived stromal cells in the tumor microenvironment might be associated with the progression of gastric cancer

Abstract

Abstract Purpose: It has been reported that the interaction between cancer cells and cancer-associated fibroblasts (CAFs) is closely associated with the progression of various types of cancer. The aim of this study is to clarify the role of bone marrow-derived stromal cells (BM-SCs), which are supposed to be the origin of CAFs in the tumor microenvironment, on the development of gastric cancer. Methods: The effect of human BM-SCs which frequently express CD271 on the proliferation and motility of six gastric cancer cell lines, OCUM-2M, OCUM-2MD3, OCUM-12, KATO-III, NUGC-3, and MKN-74, was examined. CD271 expression levels in BM-SCs were analyzed by flow cytometry. We also generated a gastric tumor model by orthotopic inoculation of OCUM-2MD3 cells in mice that had received transplantation of bone marrow from CAG-EGFP mice. The correlation between the clinicopathological features of 279 primary gastric carcinomas and CD271 expression in tumor stroma was examined by immunohistochemistry. Results: Numerous BM-SCs infiltrated the gastric tumor microenvironment; CD271 expression was found approximately 25% of BM-SCs. Conditioned medium from BM-SCs significantly increased the proliferation of gastric cancer cell lines. Furthermore, conditioned medium from gastric cancer cells significantly increased the number of BM-SCs, while migration of OCUM-12 and NUGC-3 cells was significantly increased by conditioned medium from BM-SCs. CD271 expression in stromal cells was significantly associated with macroscopic type-4 cancers, diffuse-type tumors, and tumor invasion depth. The overall survival of patients (n=279) with CD271-positive stromal cells was significantly worse than that of patients with CD271-negative stromal cells. This is the first report of the significance of BM-SCs in gastric cancer progression. Conclusions: BM-SCs were abundant in the tumor microenvironment of gastric cancer in vivo. In vitro study also indicated that the crosstalk between BM-SCs and gastric cancer cells might play an important role for the development of gastric cancer. CD271-positive tumor stromal cells might be a useful predictive prognostic factor for patients with gastric cancer. BM-SCs, therefore, might be one of therapeutic targets for cancer treatment. Citation Format: Masakazu Yashiro, Hiroaki Kasashima, Syuhei Kushiyama, Sadaaki Nishimura, Kenji Kuroda, Shingo Togano, Tomohisa Okuno, Yuichiro Miki, Tatsunari Fukuoka, Hirohisa Nakamae, Masayuki Hino, Masaichi Ohira. Bone marrow-derived stromal cells in the tumor microenvironment might be associated with the progression of gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2742.