Interleukin 8 (il-8) The Role And Significance In Early Cervical Squamous Cell Carcinoma Invasion And Metastasis

Carcinoma of the uterine cervix is the second commonest female cancer worldwide. The prevalence lies in first place in our country(China) and become one of the main disease which severely threaten health of women in our country. Lymph node metastasis is a independent prognostic factor and the main death.cause of cervical cancer patients. In order to understand carcinogenesis, development and lymph node metastasis mechanism of cervical cancer, our previous study had selected the differential expression gene by cDNA gene chip and found many genes correlated strongly with lymph node metastasis of early squamous cervical cancer. In these genes, the expression of IL-8 in early squamous cervical cancer with lymph node metastased was higer 3.4 times than with no metastatic lymph node. We speculate IL-8 plays an important role in cervical cancer invasion and metastasis.Purpose: To determine the correlation between the expression of interleukin 8(IL-8) and lymph node metastases of squamous cervical cancer and to elucidate the mechanism of IL-8-mediated invasion and metastases of earlier squamous cervical cancer and to provide a possible new clinical way for the therapy of cervical cancer.Methods: IL-8 mRNA expression was examined with reverse transcription polymerase chain reaction (RT-PCR). The expression of IL-8 protein and intratumor microvessel counts (MVC) in squamous cervical cancer were decideded respectively by antibody against IL-8 and CD-34 associated antigen and Immunohistochemical analysis. The expression of IL-8 protein in blood serum was detected ELISA.Recombinant human IL-8 stimulate cervical cancer cell(SiHa and HeLa) and Human umbilical vein endothelial cells (HUVEC) to detect IL-8-mediated cervical cancer cells and HUVEC proliferation and tumor-endothelial adhesion by MTT analysis, migration of cervical cancer cells by Boyden chamber and angiogenesis by Vitro Angiogenesis Assay Kit.To further investigate the enhance functions of IL-8 in cervical cancer, an eukaryotic expression vector pcDNA3.1(+) carrying IL-8cDNA was transiently transfected into SiHa cells by Liperfectamine 2000. The effects on proliferation and malignant of IL-8 over-expression on SiHa/pcDNA3.1/IL8 cells were evaluated by growth characteristics such as growth in anchorage-independent growth in soft agar. To evaluated the role of IL-8 in cancer metastasis, we took use of methods such as scrape-wound-migration assay and Boyden migration assay. Result: The cervical cancer with lymph node metastases express IL-8 and MVC at significantly higher level than negtive metastatic lymph node(P=0.00, 0.02). Otherwise, the express of IL-8 correlated strongly and positively with MVC of cervical cancer(r=0.251, P<0.05). Ectogenic IL-8 can stimulate cervical cancer cells and HUVEC proliferation, migration, enhance tumor-endothelial adhesion and promote capillary tube formation. IL-8 over-expressing cells...