CXCR2 signaling might have a tumor-suppressive role in patients with cholangiocarcinoma

• Published in: PloS one 2022-04, Vol.17 (4), p.e0266027-e0266027
• Main Authors: Yamamoto, Yurie, Sugimoto, Atsushi, Maruo, Koji, Tsujio, Gen, Sera, Tomohiro, Kushiyama, Shuhei, Nishimura, Sadaaki, Kuroda, Kenji, Togano, Shingo, Eguchi, Shinpei, Tanaka, Ryota, Kimura, Kenjiro, Amano, Ryosuke, Ohira, Masaichi, Yashiro, Masakazu
• Format: Article
• Language: English
• Subjects: Antibodies; Bile Duct Neoplasms - pathology; Bile Ducts, Intrahepatic - pathology; Breast cancer; Cancer; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Chemokine receptors; Chemokines; Cholangiocarcinoma; Cholangiocarcinoma - pathology; Colorectal cancer; CXCR2 protein; Gastric cancer; Genetic aspects; Health aspects; Humans; Immunohistochemistry; Ligands; Liver cancer; Lymph nodes; Lymphatic Metastasis; Medicine; Medicine and Health Sciences; Metastases; Oncology; Prognosis; R&D; Receptors, Interleukin-8B - metabolism; Regression analysis; Research & development; Research and analysis methods; Signaling; Stomach cancer; Surgery; Survival; Tumors; University graduates; Western blotting; Wound healing
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0266027

We reported that chemokine C-X-C motif receptor 2 (CXCR2) signaling appears to play an important role in the pathogenic signaling of gastric cancer (GC), and although CXCR2 may have a role in other solid cancers, the significance of CXCR2 in cholangiocarcinoma (CCA) has not been evaluated. Herein, we determined the clinicopathologic significance of CXCL1-CXCR2 signaling in CCA. Two human CCA cell lines, OCUG-1 and HuCCT1, were used. CXCR2 expression was examined by western blotting. We investigated the effects of CXCL1 on the proliferation (by MTT assay) and migration activity (by a wound-healing assay) of each cell line. Our immunohistochemical study of the cases of 178 CCA patients examined the expression levels of CXCR2 and CXCL1, and we analyzed the relationship between these expression levels and the patients' clinicopathologic features. CXCR2 was expressed on both CCA cell lines. CXCL1 significantly inhibited both the proliferative activity and migratory activity of both cell lines. CXCL1 and CXCR2 were immunohistochemically expressed in 73% and 18% of the CCA cases, respectively. The CXCL1-positive group was significantly associated with negative lymph node metastasis (p = 0.043). The CXCR2-positive group showed significantly better survival (p = 0.042, Kaplan-Meier). A multivariate logistic regression analysis revealed that CXCR2 expression (p = 0.031) and lymph node metastasis (p = 0.004) were significantly correlated with the CCA patients' overall survival. CXCR2 signaling might exert a tumor-suppressive effect on CCA cells. CXCR2 might be a useful independent prognostic marker for CCA patients after surgical resection.