J Cancer 2021; 12(4):1161-1168. doi:10.7150/jca.46765 This issue

Research Paper

Anti-fibrotic properties of an adiponectin paralog protein, C1q/TNF-related protein 6 (CTRP6), in diffuse gastric adenocarcinoma

Yoshinori Iwata1, Itaru Yasufuku1, Chiemi Saigo2, Yusuke Kito2, Tamotsu Takeuchi2✉, Kazuhiro Yoshida1

1. Department of Surgical Oncology, Gifu University, Gifu University Graduate School of Medicine, Gifu, Japan.
2. Department of Pathology and Translational Research, Gifu University Graduate School of Medicine, Gifu, Japan.

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Citation:
Iwata Y, Yasufuku I, Saigo C, Kito Y, Takeuchi T, Yoshida K. Anti-fibrotic properties of an adiponectin paralog protein, C1q/TNF-related protein 6 (CTRP6), in diffuse gastric adenocarcinoma. J Cancer 2021; 12(4):1161-1168. doi:10.7150/jca.46765. Available from https://www.jcancer.org/v12p1161.htm

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Abstract

Patients with advanced gastric cancer, especially diffuse-type gastric cancer, which is often accompanied by stromal fibrosis, commonly exhibit a poor prognosis. This study was designed to unravel the potential roles of C1q/TNF-related protein 6 (CTRP6) in the fibrotic cancer microenvironment of diffuse-type gastric adenocarcinoma. A total of 49 diffuse-type gastric cancer samples were evaluated in this study, and 23 of these samples exhibited focal CTRP6 immunoreactivity. CTRP6 immunoreactivity was found to be correlated with favorable survival outcomes, in terms of both overall and relapse-free survival rates, but this trend did not reach significance (P = 0.15). By contrast, CTRP6 immunoreactivity was significantly correlated with relapse-free survival rates in patients with diffuse-type gastric cancer at a distal site (P = 0.028). Notably, most gastric cancer cells at the cancer invasive front were CTRP6 negative, especially in areas of robust fibrosis. Double immunohistochemical staining demonstrated an inverse expression profile for CTRP6 and the activated fibroblast marker alpha smooth muscle actin (α-sma) in stromal and gastric cancer cells at the cancer invasion front. The addition of recombinant CTRP6 protein attenuated the TGF-β-induced α-sma expression in cultured human fibroblasts but did not alter the proliferation rate or Matrigel-invasion activity of the cultured gastric cancer cells. In addition, CTRP6 did not affect the viability of normal human gastric epithelial cells. This study suggests that CTRP6 may have potential application in combating stromal fibrosis in diffuse-type gastric cancers.

Keywords: CTRP6, diffuse-type gastric cancer, cancer stromal microenvironment, myofibroblast, desmoplastic reaction