CCL5/CCR5 axis promotes the motility of human oral cancer cells

Abstract

CCL5 (previously called RANTES) is in the CC-chemokine family and plays a crucial role in the migration and metastasis of human cancer cells. On the other hand, the effect of CCL5 is mediated via CCR receptor. RT-PCR and flow cytometry studies demonstrated CCR5 but not CCR1 and CCR3 mRNA in oral cancer cell lines, especially higher in those with high invasiveness (SCC4) as compared with lower levels in HSC3 cells and SCC9 cells. Stimulation of oral cancer cells with CCL5 directly increased the migration and metalloproteinase-9 (MMP-9) production. MMP-9 small interfering RNA inhibited the CCL5-induced MMP-9 expression and thereby significantly inhibited the CCL5-induced cell migration. Activations of phospholipase C (PLC), protein kinase Cdelta (PKCdelta), and NF-kappaB pathways after CCL5 treatment was demonstrated, and CCL5-induced expression of MMP-9 and migration activity was inhibited by the specific inhibitor of PLC, PKCdelta, and NF-kappaB cascades. In addition, migration-prone sublines demonstrate that cells with increasing migration ability had more expression of MMP-9, CCL5, and CCR5. Taken together, these results indicate that CCL5/CCR5 axis enhanced migration of oral cancer cells through the increase of MMP-9 production.

Restoration of dysregulated CC chemokine signaling for monocyte/macrophage chemotaxis in head and neck squamous cell carcinoma patients by neem leaf glycoprotein maximizes tumor cell cytotoxicity

“…Contrary to the monocytes, oral cancer cells, especially those with high invasiveness, express CCR5 on their surface that regulates increased migration of tumor cells and metastasis. 25 In agreement with this report, we have also detected CCR5 expression on the surface of oral tumor cells obtained from oral cancer tissue and cell lines. This differential CCR5 expression in immune cells versus tumor cells seems to be associated with suboptimal circulation of immune cells towards a chemotactic gradient from the tumor site.…”

Autocrine CCL5 Signaling Promotes Invasion and Migration of CD133 + Ovarian Cancer Stem‐Like Cells via NF‐κB‐Mediated MMP‐9 Upregulation

“…MMP-9 has been implicated in many types of cell translocation, including invasion of tissues by tumor cells, T cells, and dendritic cells [26,27]. Furthermore, it has been postulated in previous studies that MMP-9 is involved in CCL5-directed cell migration [27,28,29]. We thus hypothesized that MMP-9 may be involved in CCL5/CCR1-and/or CCR3-mediated CSLC migration and invasion.…”

Anti–IL-20 Monoclonal Antibody Alleviates Inflammation in Oral Cancer and Suppresses Tumor Growth

“…A variety of cytokines, such as IL-1, IL-6, and TNF-a, as well as chemokines, such as IL-8, CXCL5, CXCL6, CXCL7, CCL5, and CCL20, were upregulated in progressive oral cancer cells (6,37,38) and in patients with oral cancer (13). The effects of CCL and CXCL chemokines are mediated via their CCR and CXCR receptors.…”