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.
Highlights
Cancer progression and metastasis are controlled by the tumor microenvironment and do not depend solely on cancer cell-autonomous defects [1, 2]
The interaction between cancer cells and cancer-associated fibroblasts (CAFs) has been suggested to be important for the progression of some types of cancer [4,5,6], and we demonstrated that some amount of CAFs in the stroma of gastric cancer originated from bone marrow-derived mesenchymal cells (BM-MCs) [7]
Another of our studies demonstrated that chemokine (C-X-C motif) ligand 1 (CXCL1), which is produced from diffuse-type gastric cancer (DGC) cells, is closely associated with the recruitment of BM-MCs into tumor stroma via chemokine (C-X-C motif) receptor 2 (CXCR2) of BM-MCs [8]
Summary
Cancer progression and metastasis are controlled by the tumor microenvironment and do not depend solely on cancer cell-autonomous defects [1, 2]. We observed that the stromal expression of CD271, which is one of the markers of BM-MCs, was a useful prognostic factor for gastric cancer patients [7]. Another of our studies demonstrated that chemokine (C-X-C motif) ligand 1 (CXCL1), which is produced from diffuse-type gastric cancer (DGC) cells, is closely associated with the recruitment of BM-MCs into tumor stroma via chemokine (C-X-C motif) receptor 2 (CXCR2) of BM-MCs [8]. Several research groups reported that CXCL1 [9, 10] and CXCR2 [11, 12] were poor prognostic factors in studies using human samples of several types of cancers including gastric cancer, colorectal cancer, and pancreatic cancer. We extended the scope of our research to determine the significance of the CXCL1-CXCR2 axis in the tumor microenvironment of gastric cancer
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