chemokine receptor CXCR4-expression in oral cancer cells

CXCR4 is a G-protein-coupled receptor that specifically hinds to the a-chemokine Stromal CellDerived Factor-I [SDF-1]. SDF- I and CXCR4 represent a unique ligand /receptor pair that plays a crucial role in embryological development, leukocyte development and migration, metastases of tumours and the entry of HIV into T lymphocytes. Expression and importance of CXCR4 has been established in a wide range of malignant conditions. The aim of this study was to establish the expression of CXCR4 in oral cancer cells and whether this expression differed from that of cells derived from normal oral tissue. An enzyme linked immunosorbent assay [LL1SA] was performed to determine and compare the expression of CXCR4 at the messenger RNA [mRNA] level. Receptor expression at protein level was established by means of lmmunocytochemistry. Six different cancer cell lines [derived from Oral Squamous Cell Carcinoma] were used along with human gingival fibroblasts as a positive control [since they have been shown to express CXCR4]. The SVpgC2a cell line consistently expressed CXCR4, however, the mRNA expression of CXCR4 in almost all cancer cell lines was found to be significantly greater when compared to the SVpgC2a cell line. The potential influence of Foetal Bovine Serum [FBS] on CXCR4 expression was also investigated by exposing all the cell types to their respective serum-free media. No discernible difference in CXCR4 expression was observed, leading to the observation that FBS did not alter CXCR4 expression. These findings were complimented by the CXCR4 protein expression detected by immunocytochemistry. indicating CXCR4 staining on the SVpgC2a cell line to be much less than all the cancer cell lines, regardless of FBS exposure. These results suggest that normal oral keratinocytes may express the CXCR4 receptor and that expression may be up-regulated in conditions of malignancy. These findings suggest that CXCR4 may have a potential role in the metastasis of oral cancer

Expresions of the chemokine receptor CXCR4 by cancer cells literature review

Metastasis is the main cause of morbidity and mortality in cancer patients. However, the precise mechanism has stood unknown for a long time. The 'chemo-attraction' theory implies that organ-specific attractant molecules enter the circulation, facilitating the humour cells to invade through the blood vessels and thus enter the organs. Chemokines and their receptors play a vital role in leukocyte trafficking and homeostasis and fulfill many of the criteria important in the chemoattraction theory of tumour metastasis. Miller et al [2001] fashioned a series of experiments to study whether chemokine/chemokine receptor interactions play any part in the metastasis of breast cancer. Their findings validated the 'chemoattraction theory' of metastasis and revealed significant upregulation of the G-protein coupled chemokine receptor CXCR4 by, the malignant breast epithelial cells compared to their normal counterparts. The a-chemokine Stromal CellDerived Factor-I [SDF- 1] which is the ligand/chemokine for CXCR4, was also found to be secreted in greater quantities by the target metastatic sites in accordance with the hypothesis. This suggested a potential role of CXCR4/SDF- I interaction in metastasis. Experiments carried out with other malignancies have corroborated the findings of Miller et al. Studies on malignant melanoma, leukaemia, lymphoma and cancers of lung, ovary, prostate, kidney, brain and thyroid, have revealed up-regulated expression of CXCR4 and it's ligand SDF-1. The expression and role of CXCR4 in oral cancers remains unidentified. It might be interesting to investigate whether CXCR4/SDF-1 interaction has any role in the metastasis of oral cancers to the regional lymph nodes