Expression Of CXCR4 And MMP-9 In Esophageal Cancer

Backgroud and ObjectiveInfiltration and metastasis are not only the major characteristic of the malignant tumor, but also the key to its hard curing and the resulting death of patients. Chemotatic factor is cell factor having chemotaxis through cell secretion by different groups of a macro-category, and it is a haplo-chain micromolecule (8-10kD) protein superfamily, including CC, CXC, XC and CX3C four families respectively. Chemotatic factor acceptor accordingly is divided as CCR, CXCR, XCR and CX3CR according to the connection with different categories. Chemotatic factor acceptor is over-expression not only on immunocell, but on some tumor cells. Muller stated firstly the relationship of chemotatic factor acceptor and breast cancer metastasis in 2001, and discovered that it has been close correlation with tumor metastasis. Moreover, Chemotatic factor acceptor also was found to play very important effects in the growth, invasion and metastasis of multi-species malignant tumors. Therefore, it has become the new attracting target in the research of antitumor drug. CXCR4 is not tumor specificity marker, but it shows overexpression in many tumors. Many researches report that CXCR4 plays very important effects in the tumor-genesis, infiltration, metastasis, myxo-adnexal and externalization. But contraries exists in the present researches, without final conclusions to some questions. During the process of tumor metastasis, the first step is breaking through the barriers of basement membrance and extra cellular matrix. The main ingredients of BM and ECM included two components, one is structural proteins, which composed with collagen, laminin, fiber light beam and beam with vitrectomy et al. The corresponding enzyme is MMPs, which play a important role in the process of tumor invasion and metastasis. MMPs is a big family, MMP-2 and MMP-9 are more closely with tumor invasion and metastasis among the members. Studies have shown that MMP-9 play a key role in the process of the cell-mediated tumor cell extracellular matrix degradation.Presently there are only a few studies on the expression of CXCR4 in ESCC at abroad and there are no related reports at home. The relation between CXCR4 and ESCC is unclear. In order to discuss the correlation of genes of CXCR4 and MMP-9 with growth and trans-infiltration of esophageal squamous cell carcinoma (ESCC), find the targets of early detecting ESCC growth and metabasis, and explore the effetive way which could prevent its growth and metabasis, we detect mRNA and protein expression levels of CXCR4 and MMP-9 in ESCC by in situ hybridization and immunohistochemical staining, analysis the relationship between CXCR4 and MMP-9 and between them and invasion and metastasis of ESCC.Material and methods1. The immunohistochemical staining was used to measure the protein expression of CXCR4 and MMP9 in 62 cases of ESCC,62 cases of normal esophageal mucosa and 31 cases of adjacent atypical hyperplasia tissues.2. In situ hybridization was used to detect the mRNA expression of CXCR4 and MMP9 in 62 cases of ESCC,62 cases of normal esophageal mucosa and 31 cases of adjacent atypical hyperplasia tissues.3. Statistical analysis was carried out using Statistical Package for Social Sciences(SPSS)P, version 13.0 for windows. Chi-square test, one-way anaysis of variances and two indepndent-samples t test were used. P-values of<0.05 were considered to be statistically significant..Result1. The positive rates of CXCR4 protein(59.7%) and mRNA(74.2%) in ESCC were significantly higher than in adjacent atypical hyperplasia(35.5%,40.9%) and in normal esophageal mucosa(25.8%,24.0%). There were significant differences in the expressions of CXCR4 among the three groups(P<0.05).2. The positive rates of CXCR4 protein(68.2%) and mRNA(85.4) with tumor invaded into fiber membrane were significantly higher than those with tumor invaded into deep muscle layer(57.1%,64.3%)and tumor invaded into shallow muscle layer(14.3%,28.6%). The differences among the three groups were statistically significant (P< 0.05).3. With the increase of histological grade, CXCR4 mRNA(77.3%,72.0%and 73.3%) and protein(63.6%,56.0%and 60.0%) expression was no significant change. There were no significant differences among different groups(P>0.05).4. The positive rate of CXCR4 protein(85.0%) and mRNA(95.0%) with lymph node metastasis were significantly higher than those without lymph node metastasis(47.6%,64.3%). The difference between the two groups was statistically significant (P<0.05).5. The positive rates of MMP-9 mRNA(72.6%) and protein(80.6%) in ESCC were significantly higher than in adjacent atypical hyperplasia(51.6%,58.1%) and in normal esophageal mucosa(41.9%,27.4%). There were significant differences in the expressions of MMP-9 among the three groups(P<0.05).6. The positive rates of MMP-9 mRNA(80.5%) and protein(92.7%) with tumor invaded into fiber membrane were significantly higher than those with tumor invaded into deep muscle layer(71.4%,71.4%) and tumor invaded into shallow muscle layer(28.6%,28.6%). The differences among the three groups were statistically significant (P<0.05).7. With the increase of histological grade, MMP-9 mRNA(53.5%,68.0%and 90.9%) and protein(46.7%,88.0%and 95.5%) expression was significant changed. There were significant differences among different groups(P>0.05).8. The positive rate of MMP-9 mRNA(95.0%) and protein(100.0%) with lymph node metastasis were significantly higher than those without lymph node metastasis(61.9%and 71.4%). The difference between the two groups was statistically significant (P<0.05). 9. There was a positive correlation between the mRNA and protein expressions of CXCR4 and MMP-9 in ESCC. (P<0.05)Conclusion1. CXCR4 and MMP-9 may play an important role in the process of invasion and metastasis of ESCC.2. CXCR4 and MMP-9 protein expressions were positively correlated, suggesting that they has a certain synergy in the development of ESCC.3. The mRNA expression and protein expression of CXCR4 and MMP-9 were consistent.