Sun Chao, Fukui Hirokazu, Hara Ken, Zhang Xinxing, Kitayama Yoshitaka, Eda Hirotsugu, Tomita Toshihiko, Oshima Tadayuki, Kikuchi Shojiro, Watari Jiro, Sasako Mitsuru, Miwa Hiroto
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, l-1, Mukogawa, Nishinomiya, 663-8501, Japan.
Department of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin, China.
BMC Cancer. 2015 Apr 30;15:333. doi: 10.1186/s12885-015-1353-3.
Cancer-associated fibroblasts (CAFs), which reside around tumor cells, are suggested to play a pivotal role in tumor progression. Here we performed microarray analyses to compare gene expression profiles between CAFs and non-cancerous gastric fibroblasts (NGFs) from a patient with gastric cancer and found that fibroblast growth factor 9 (FGF9) was a novel growth factor overexpressed in CAFs. We then examined the biological effects of FGF9 during progression of gastric cancer.
Expression of FGF9 in CAFs and NGFs, and their secreted products, were examined by Western blotting. The effects of FGF9 on AGS and MKN28 gastric cancer cells in terms of proliferation, invasion and anti-apoptosis were assessed by WST-1 assay, invasion chamber assay and FACS, respectively. Furthermore, the intracellular signaling by which FGF9 exerts its biological roles was examined in vitro.
FGF9 was strongly expressed in CAFs in comparison with NGFs, being compatible with microarray data indicating that FGF9 was a novel growth factor overexpressed in CAFs. Treatment with FGF9 promoted invasion and anti-apoptosis through activation of the ERK and Akt signaling pathways in AGS and MKN28 cells, whereas these effects were attenuated by treatment with anti-FGF9 neutralizing antibody. In addition, FGF9 treatment significantly enhanced the expression of matrix metalloproteinase 7 (MMP7) in both cell lines.
FGF9 is a possible mediator secreted by CAFs that promotes the anti-apoptosis and invasive capability of gastric cancer cells.
肿瘤相关成纤维细胞（CAFs）存在于肿瘤细胞周围，被认为在肿瘤进展中起关键作用。在此，我们进行了微阵列分析，以比较一名胃癌患者的CAFs与非癌性胃成纤维细胞（NGFs）之间的基因表达谱，发现成纤维细胞生长因子9（FGF9）是一种在CAFs中过表达的新型生长因子。然后，我们研究了FGF9在胃癌进展过程中的生物学效应。
通过蛋白质印迹法检测FGF9在CAFs和NGFs及其分泌产物中的表达。分别通过WST-1法、侵袭小室法和流式细胞术评估FGF9对AGS和MKN28胃癌细胞增殖、侵袭和抗凋亡的影响。此外，在体外研究了FGF9发挥其生物学作用的细胞内信号传导。
与NGFs相比，FGF9在CAFs中强烈表达，这与微阵列数据一致，表明FGF9是一种在CAFs中过表达的新型生长因子。用FGF9处理通过激活AGS和MKN28细胞中的ERK和Akt信号通路促进侵袭和抗凋亡，而用抗FGF9中和抗体处理可减弱这些作用。此外，FGF9处理显著增强了两种细胞系中基质金属蛋白酶7（MMP7）的表达。
FGF9是CAFs分泌的一种可能的介质，可促进胃癌细胞的抗凋亡和侵袭能力。
