CXCR2 Signaling Appears to Have Implications for Cholangiocarcinoma

A new report identifies a chemokine receptor that may be an important indicator of patient prognosis in cholangiocarcinoma (CCA).

The finding is based on an analysis published this month in PLoS One.

The authors, from the Osaka City University Graduate School of Medicine, in Japan noted that because CCA is often not diagnosed until an advanced stage, patients tend to have a poor prognosis. However, recent work raises hope of reliable biomarkers, which in turn could lead to earlier detection, more personalized therapy, and potentially better outcomes.

Much of the latest research has focused on the role of chemokines in the development of CCA and other cancers. The authors noted that chemokine C-X-C motif receptor 2 (CXCR2) has become a target receptor in several cancer types, although its impact on tumors may differ from among cancer types.

In gastric cancers, the investigators said CXC-motif ligand 1, one of the ligands for CXCR2, may play a particularly important role. “These findings suggest that CXCL1-CXCR2 signaling may exert one or more actions in the development of CCA,” they wrote.

In their new study, they examined the potential significance of CXCL1-CXCR2 signaling by beginning with 2 human CCA cell lines and using western blotting to examine CXCR2 expression. They then used MTT and wound-healing assays to understand how CXCL1 influences the proliferation and migration activity of the cell lines. Next, they conducted a retrospective immunohistochemical study on 178 patients with CCA who underwent surgery at Osaka City University Hospital. The investigators wanted to quantify CXCR2 and CXCL1 expression levels and then compare those expression levels to patient outcomes and characteristics.

The analysis showed that CXCR2 was present in both of the cell lines the investigators examined (OCUG-1 and HuCCT1) and that CXCL1 had the effect of inhibiting both proliferative and migratory activity, they said.

When the investigators turned to the study of CCA cases, immunohistochemical results showed 73% of patients had CXCL1 expression, but just 18% had CXCR2 expression. The patients with CXCL1 expression were less likely to have distant metastasis (P = .043), the authors said.

“CXCL1 may inhibit distant metastasis by suppressing the migratory potential of CCA cells,” they wrote. “These results suggest that CXCL1 may act as a suppressor of CCA progression.”

The authors then noted that other members of the CXCR2 ligand family, including CXCL5 and CXCL7, have been reported to be associated with CCA progression. These findings suggest that CXCL1 might have the opposite effect.

Meanwhile, they also found an apparent link between CXCR2 expression and survival. Patients who were positive for CXCR2 expression had higher survival rates, according to both Kaplan-Meier curves (P = .042) and multivariate logistic regression analysis (P = 0.031).

“These findings suggested that CXCR2 might be a useful independent prognostic marker for CCA patients after surgical resection,” the authors wrote.

Taken together, they said the study affirms that CXCR2 signaling is an important research area in gastric cancers.

Reference

Yamamoto Y, Sugimoto A, Maruo K, et al. CXCR2 signaling might have a tumor-suppressive role in patients with cholangiocarcinoma. PLoS One. Published online April 4, 2022. doi:10.1371/journal.pone.0266027