Clinicopathologic significance of the CXCL1-CXCR2 axis in the tumor microenvironment of gastric carcinoma

Abstract

PurposeIt was reported that the chemokine (C-X-C motif) ligand 1 (CXCL1) from cancer cells stimulated the recruitment of bone marrow-derived mesenchymal cells (BM-MCs) into tumor stroma via chemokine (C-X-C motif) receptor 2 (CXCR2) signaling. We conducted this retrospective study to determine the clinicopathologic significance of the CXCL1-CXCR2 axis in human gastric cancer.MethodsThe correlations between the clinicopathological features of 270 primary gastric carcinomas and CXCL1 in cancer cells and CXCR2 in stromal cells were analyzed in immunohistochemical studies. The effect of gastric cancer cells on the expression of CXCR2 in BM-MCs was examined using diffuse-type gastric cancer cell lines in vitro.ResultsThe expression of CXCL1 in cancer cells was correlated with T invasion (T2–T4), lymph node metastasis, lymphatic invasion, venous invasion, peritoneal cytology, peritoneal metastasis and CXCR2 expression in stromal cells. The expression of CXCR2 in stromal cells was correlated with macroscopic type-4 cancers, histological type, T invasion (T2–T4), lymph node metastasis, lymphatic invasion, infiltration, peritoneal cytology, peritoneal metastasis and CD271 expression in stromal cells. The overall survival of patients with CXCL1 and CXCR2-positive cancer was poorer than that of the patients with negative cancer. Both CXCL1 expression in cancer cells and CXCR2 expression in stromal cells were independent prognostic factors for gastric cancer patients.ConclusionThe expressions of CXCL1 in cancer cells and CXCR2 in stromal cells are useful prognostic factors for gastric cancer patients.

CXCL1/CXCR2 Paracrine Axis Contributes to Lung Metastasis in Osteosarcoma

“…Recent evidence has demonstrated that tumor-secreted CXCL1 enhances tumor growth via the recruitment of various inflammatory cells [16,39] or stroma cells [40,41] into the tumor microenvironment via paracrine or autocrine mechanisms. We are the first to provide evidence showing that HPAECs-induced secretion of CXCL1 recruits CXCR2-expressing osteosarcoma cells to pre-metastatic pulmonary sites.…”

Interaction between Tumor-Associated Dendritic Cells and Colon Cancer Cells Contributes to Tumor Progression via CXCL1

“…CXCL1 is upregulated in various cancers and associated with cancer progression, such as cancer cell growth, proliferation, tumor angiogenesis and metastasis, after the activation of CXCR2 [27,28,29]. In addition, CXCL1 is not only involved in cancer progression, but also responsible for resistance to several chemotherapeutic drugs, such as oxaliplatin, doxorubicin, and cyclophosphamide [30,31,32,33].…”

Prognostic and Clinicopathological Significance of CXCL1 Expression in Gastric Cancer: A Meta-Analysis.

“…As a result, 23 studies remained for full-text screening, 14 studies were excluded under the following exclusion criteria: 5 studies for reviews and 9 studies for insu cient data. Finally, 9 studies involving a total of 1474 patients were included [18,19,[21][22][23][26][27][28][29]. The ow diagram of literature retrieval was shown in Fig.…”