Abstract 2045: A factor (&gt; MR 30 kDa) from cancer-associated fibroblasts may stimulate the progression of schirrous gastric cancer without FGFR2 overexpression
Authors: Kushiyama Syuhei , Yashiro Masakazu , Okuno Tomohisa , Kuroda Kenji , Tanaka Ryota , Togano Shingo , Nishimura Sadaaki , Toyokawa Takahiro , Tanaka Hiroaki , Muguruma Kazuya , Hirakawa Kosei , Ohira Masaichi 
Published: August 2019

Purpose: Scirrhous gastric cancer (SGC), diffusely infiltrating carcinoma, proliferate rapidly with fibrosis, when the cancer cells invade into the submucosa of the stomach. It has been reported that the interactions between the cancer cells and stromal cells, such as cancer-associated fibroblasts (CAFs), surrounding them advance the proliferation and invasion of some types of solid carcinomas. We previously clarified that fibroblast growth factor-7 (FGF7) produced by CAFs promotes the proliferation and tumor progression of SGC. However, the FGF receptor type 2 (FGFR2), which is a specific receptor of FGF7, is just expressed on only 20% of SGC, suggesting that about 80% of growth-stimulating signaling by the interaction between the SGC cells and CAFs might be different from FGF7/FGFR2 signaling.

Materials and Methods: In this study, we aim to clarify the interaction between SGC cells and CAFs except FGF7/FGFR2 signaling in the tumor progression of SGC. We used 4 SGC cell lines, OCUM-1, OCUM-8, OCUM-9, and OCUM-12, which do not overexpress FGFR2. Five CAF cell lines, CAF82, CAF88, CAF90, CAF91, and CAF92, were established by a primary culture from individual gastric carcinoma specimens. Serum-free conditioned medium (SF-CM) from CAFs was added to each SGC cell lines and evaluate them. The interaction of SGC and SF-CM was analyzed by CCK assay and the wound healing assay. The humoral factors in SF-CM which stimulate the proliferation of SGC is divided according to the size of the molecular weight and evaluated by the CCK assay.

Results: CCK assay revealed that CAF82 SF-CM promoted the proliferation of OCUM-9 and OCUM-12 by each 27 % and 20 %. CAF88 SF-CM promoted the proliferation of OCUM-9 by 17 %. CAF90 SF-CM promoted the proliferation of OCUM-1 and OCUM-9 by each 33 % and 21 %. CAF91 SF-CM promoted the proliferation of OCUM-1 and OCUM-9 by each 29 % and 25 %. CAF92 SF-CM promoted the proliferation of OCUM-1 and OCUM-9 by each 37% and 5 %. According to the wound healing assay, the invasion activity of OCUM-12 was promoted by SF-CM from CAF82, CAF90, CAF91, and CAF92 by each 56%, 37%, 34%, and 52%. CAF82 SF-CM which contain humoral factors that molecular weight is more than 30kDa promote the proliferation of OCUM-12 by 16%.

Conclusion: The factors over 30kDa from CAF might stimulate the progression of SGC cells without FGFR2 expression.

Citation Format: Syuhei Kushiyama, Masakazu Yashiro, Tomohisa Okuno, Kenji Kuroda, Ryota Tanaka, Shingo Togano, Sadaaki Nishimura, Takahiro Toyokawa, Hiroaki Tanaka, Kazuya Muguruma, Kosei Hirakawa, Masaichi Ohira. A factor (&gt; MR 30 kDa) from cancer-associated fibroblasts may stimulate the progression of schirrous gastric cancer without FGFR2 overexpression [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 2045.