Chemokine Receptor (CXCR4/CCR7) Association With Oral Squamous Cell Carcinoma

Backgroud and object: Oral squamous cell carcinoma occur on the cutaneous surface of the face and mucous membrane of the mouth. It is a most common Oral and Maxillofacial malignancy, and the incidence rate of OSCC has a trend to elevation in china in recent years. Most of the patients who had a final diagnosis of were too late to accept radical prostatectomy, and the therapeutic efficacy was far from satisfication. Cancer invasion and metastasis is the major cause of deaths of OSCC, cervical lymph node is a most common target organ. Chemokines belong to the small molecule chemoattractive cytokine family. Recent studies showed that chemokines and their receptor are significantly associated with invasion and lymph node mtastasis of tumors. Stromal cell-derived factor-1(SDF-1) and its receptor CXCR4 (chemokine CXC motif receptor 4) and chemokine CC motif ligand 19 (CCL19) or chemokine CC motif ligand 21 (CCL21) and its receptor CCR7 (chemokine CC motif receptor 7) in tumor metastasis to special organ is being noticed. CXCR4 and CCR7 hightly overexpresses in breast cancer, melamna, gastric carcinoma, nonsmall cell lung cancer, osteosarcoma tumor, glioblastoma and rhabdomyosarcoma cells, SDF-1 and CCL19/CCL21 overespresses in several special organs Which "atract" tumor cells and lead to organ metastases eventually. These findings suggest that SDF-1/CXCR4 and CCL19/CCR7 or CCL21/CCR7 plays a critical role in tumor cells selective metastases. The aims of this study were to observe the expression of CXCR4 and CCR7 in primary tumor cells of Oral squamous cell carcinoma(OSCC )and the tumor cells of the regional metastasized lymph nodes and nomal mucous membrane of the mouth tissue, and to evaluate the possible correlation between the expression of CXCR4 and CCR7 and the clinicopathology factors, and cervical lymph node metastasis of OSCC and further to explore the role of CXCR4,CCR7 in cervical lymph nodes metastasis in OSCC.Methods The expression of CXCR4 and CCR7 in 64 cases of OSCC(included 39 cases of lymph node metastasis of OSCC), 10 cases of reactive hyperplasia of lymph node of neck ,10 cases of nomal mucous membrane of the mouth tissue were detected by immunohistochemistryand in situ hybridization, and its relation to cliniopathological data and cervical lymph node metastasis of OSCC was also analyzedResults 1. CXCR4 mRNA and CXCR4 was positively expressed in OSCC, and the positive expression rate of CXCR4 protein was 62.5%(40/64). In addition, expression of CXCR4 protein was also correlated with tumor histological type (P=0.0042), depth of invasion (P<0.001),lymphatic invasion (P<0.001), and TNM stage (P=0.0012), but not with age at surgery, gender and tumor size. Respectively.2. CCR7 mRNA and CCR7 was positively expressed in OSCC, and the positive expression rate of CCR7 protein was 65.6%(42/64). Meanwhile,expression of CCR7 protein was also correlated with tumor histological type (P=0.027), depth of tumor invasion ( P<0.001 ) , lymphatic invasion (P<0.001), and TNM stage (P<0.001), but not with age at surgery, gender, tumor size.3. CXCR4 mRNA and CXCR4 was positively expressed the tumor cells of the regional metastasized lymph nodes in OSCC, and the positive expression rate of CXCR4 protein was 74.4%(29/39). In addition, CXCR4 expression was significantly higher in the patients with lymph node metastasis than those without lymph node metastasis (P=0.0144). and stepwise regression analysis revealed that the most important factor related to lymph node metastasis was the expression of CXCR4.4. CCR7 mRNA and CCR7 was positively expressed the tumor cells of the regional metastasized lymph nodes in OSCC, and the positive expression rate of CCR7 protein was 84.6%(33/39). Meanwhile, CCR7 expression was significantly higher in the patients with lymph node metastasis than those without lymph node metastasis (P<0.001), and stepwise regression analysis revealed that the most important factor related to lymph node metastasis was the expression of CCR7.Conclusions CXCR4 and CCR7 is positive expressed in primary tumor cells of Oral squamous cell carcinoma(OSCC )and the tumor cells of the regional metastasized lymph nodes , and its expression was associated with the diverse progression of OSCC, including invasion and lymph node metastasis. CXCR4 and CCR7 as a potential therapeutic target in advanced cases of oral squamous cell carcinoma. Those data provide foundation for further study on the molecular mechanism of invasion and cervical lymph node metastasis of OSCC.