CXCL5 and its
receptor CXCR2 have been found to be involved in tumorigenesis and
cancer progression. Recent studies have shown that CXCR2 is upregulated in
glioma tissues, and associated with poor prognosis and recurrence. However, the role of CXCL5/CXCR2 signaling in mediating the malignant phenotypes of
glioma cells, as well as the underlying mechanism, still remains unclear. In the present study, we found that CXCL5 was upregulated in
glioma tissues compared to that noted in normal brain tissues. High CXCL5 levels were significantly associated with higher
tumor grade, advanced clinical stage, and shorter survival time of
glioma patients. In vitro studies indicated that the
protein expression levels of CXCL5 and CXCR2 were markedly higher in human
glioma cell lines (U87, U251, U373 and A172), when compared with those in normal human gliocyte HEB cells. Overexpression of CXLC5 significantly promoted the proliferation and migration of U87 cells, while knockdown of CXCL5 by
small interfering RNA markedly inhibited U87 cell proliferation and migration. Moreover, both exogenous CXCL5 treatment and the
conditioned medium of CXCL5-overexpressing HEB cells also enhanced the proliferation and migration of U87 cells. Molecular mechanism investigation revealed that CXLC5 activated the ERK, JNK,
p38 MAPK signaling pathways, which play key roles in
tumor growth and
metastasis. According to these data, our study suggests that CXCL5 plays a promoting role in
glioma in autocrine- and paracrine-dependent manners.