CXCR2 signaling might have a tumor-suppressive effect on cholangiocarcinoma cells, a new study published in PLOS One found. CXCR2 therefore might be a useful independent prognostic marker for patients with cholangiocarcinoma following surgery.

It was previously known that CXCR2 signaling is involved in gastric cancers and other solid cancers. However, its potential role in cholangiocarcinoma had not been elucidated.

In the present study, a team of researchers led by Masakazu Yashiro, MD, PhD, from Osaka City University Graduate School of Medicine in Japan used 2 human cholangiocarcinoma cell lines to analyze the effect of CXCR2 signaling on cell proliferation and migration.

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The researchers first reported that CXCR2 was expressed on both cell lines and that CXCL1, one of CXCR2’s ligands, significantly inhibited the proliferation and migration of both cell lines. They also analyzed 178 patients with cholangiocarcinoma and showed that 73% of them expressed CXCL1 while 18% expressed CXCR2.

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“The CXCL1-positive group was significantly associated with negative lymph node metastasis,” the researchers said, and that the CXCR2-positive group demonstrated better survival. Statistical analyses showed that CXCR2 expression and lymph node metastasis were significantly correlated with overall survival.

Cholangiocarcinoma is a group of heterogeneous malignant tumors originating from the cells of the biliary tree. The etiology of the disease is unknown, although there are some risk factors associated with the development of the disease such as pre-existing conditions including primary sclerosing cholangitis, Caroli’s and type 1 and 4 biliary cysts, and viral and parasitic infections.

CXCR2 or chemokine C-X-C motif receptor 2 is a prominent chemokine receptor found on neutrophils. The receptor has many ligands and previous research has shown that CXCL7 and CXCL5 play a role in the development of cholangiocarcinoma. The findings of this study underscore the potential of CXCL1-CXCR2 signaling in cholangiocarcinoma tumor suppression. 


Yamamoto Y, Sugimoto A, Maruo K, et al. CXCR2 signaling might have a tumor-suppressive role in patients with cholangiocarcinoma. PLOS One. 2022;17(4):e0266027. doi:10.1371/journal.pone.0266027