Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka, Japan.
Anticancer Res. 2022 Jan;42(1):501-509. doi: 10.21873/anticanres.15508.
BACKGROUND/AIM: Cancer-associated fibroblasts (CAFs) may promote the malignancy of human scirrhous gastric cancer (SGC) cells. We conducted the present study to identify novel growth factors from CAFs.
OCUM-12 and 2 CAF cell lines were used. The proliferation of cancer cells was determined by the number of cancer cells or the MTT assay. The growth factor(s) were purified and characterized by the gel filtration chromatography and protein array.
The molecular weight of the growth-stimulating factor was estimated to be approximately 66-669 kDa. Protein array of conditioned medium (CM) from CAFs indicated that dipeptidyl peptidase-4 (DPP-4) was one of the growth factors. The addition of CM increased the phosphorylation of C-X-C chemokine receptor 4 (CXCR4). The DPP-4 inhibitor significantly inhibited the growth-stimulating activity of CM.
DPP-4 from CAFs might be one of the growth-stimulating factors for SGC through CXCR4.
背景/目的：癌相关成纤维细胞（CAFs）可能促进人类硬癌（SGC）细胞的恶性转化。本研究旨在从 CAFs 中鉴定新的生长因子。
使用 OCUM-12 和 2 CAF 细胞系。通过癌细胞数量或 MTT 测定确定癌细胞的增殖。通过凝胶过滤层析和蛋白质阵列纯化和表征生长因子。
生长刺激因子的分子量估计约为 66-669 kDa。CAFs 条件培养基（CM）的蛋白质阵列表明二肽基肽酶-4（DPP-4）是生长因子之一。CM 的添加增加了 C-X-C 趋化因子受体 4（CXCR4）的磷酸化。DPP-4 抑制剂显著抑制 CM 的生长刺激活性。
来自 CAFs 的 DPP-4 可能通过 CXCR4 成为 SGC 的生长刺激因子之一。
