The migration, adhesion, and proliferation of conceptuses during pregnancy are tightly controlled processes that are mediated by various factors including cytokines, growth factors, and hormones. Among many factors, chemokines play key roles in lymphocyte trafficking, cellular proliferation, vascularization, and embryogenesis in many mammalian species. Especially, it has been shown that C-X-C chemokine ligand 12 (CXCL12) plays an important role in early pregnancy by promoting trophoblast invasion, proliferation, and differentiation through its receptor, C-X-C chemokine receptor 4 (CXCR4) in humans. However, expression and function of CXCL12 in the uterine endometrium during pregnancy have not been well studied in pigs. Thus, we determined expression of CXCL12 and its receptor, CXCR4, in the uterine endometrium during the estrous cycle and pregnancy in pigs. We obtained endometrial tissues from gilts on day (D) 12 and D15 of the estrous cycle and D12, D15, D30, D60, D90, and D114 of pregnancy, conceptus tissues from D12 and D15 of pregnancy, and chorioallantoic tissues from D30, D60, D90, and D114 of pregnancy. Real-time RT-PCR analysis showed that levels of CXCL12 and CXCR4 mRNAs changed in the uterine endometrium during pregnancy. Levels of CXCL12 and CXCR4 mRNAs on D15 of pregnancy were higher than those on D15 of the estrous cycle. After D15 of pregnancy levels of CXCL12 and CXCR4 mRNAs gradually decreased toward term of pregnancy, and CXCL12 and CXCR4 were expressed in the chorioallantoic tissues during the mid- to late pregnancy. CXCL12 and CXCR4 mRNAs were expressed in chorioallantoic tissues during mid- to late pregnancy, and RT-PCR analysis showed that CXCL12 and CXCR4 mRNAs were detectable in conceptus on D12 and D15 of pregnancy. Immunohistochemistry showed that CXCL12 proteins were localized to endometrial luminal and glandular epithelial cells during the estrous cycle and pregnancy, and to chorionic epithelial cells during mid- to late pregnancy. Abundance of CXCL12 mRNAs, but not CXCR4, in the uterine endometrium was increased by the treatment of IFNG. These results showed that CXCL12 and CXCR4 were expressed in the uterine endometrium, conceptus, and chorioallantoic tissues and IFNG increased endometrial CXCL12 expression in pigs, suggesting that CXCL12 and its receptor may play a key role in regulation of the establishment and maintenance of pregnancy by affecting the conceptus development in pigs. [supported by the Next Generation BioGreen 21 Program (#PJ01110301), Rural Development Administration]
The support mechanisms that are involved in lymph node metastasis of oral squamous cell carcinoma remain largely unknown. Recent studies have demonstrated that tumor cells express chemokine receptors and use chemokines to metastasize to the target organ in many malignancies in humans There are few reports about the correlation between chemokin receptor CXCR-4 expression and clinicopathologic factors in oral squamous cell carcinomas. The object of this study was to evaluate the availabili ty of CXCR-4 expression as prognostic marker through correlation analysis of CXCR-4 expression in oral sq uamous cell carcinoma and its r elation to clinocopathologic factors and PCNA index. 80 we investigated CXCR-4 expression of 74 oral squamous cell carcinomas by immunohistochemistry. 44 out of 74 cases(59. 5%) showed CXCH-4 positive and 30 sampl es(40.5%) showed CXCH-4 negative. CXCH-4 expression showed statistically sig nificant correlation wi th lymph node metastasis(p=0.026) ‘ PCNA index (p=0.003) , survial rate(p=0.0003). From the results , it was suggested CXCR-4 oxpression might be useful a prognostic marker in oral squamous cell carClllomas
Although a number of molecules have been implicated in the metastasis of oral squamous cell carcinoma (OSCC) , the precise molecular mechanisms that deterrnine the direction of rnigration and invasiveness of OSCC cells into the lymph nodes remain unclear, Chemokines are a superfarnily of small structurally related heparin- binding proteins‘ which have been identified as attractants that control the rnigration of leukocytes‘ especia lly during imrnune and inflammatory reactlOns Moreover, recent studies have demonstrated that several types 。f cancer express chemokine receptor‘s and use chemokines to metastasize to the target organ, However, there h ave been few reports on biological behaviors by downregulation 0 1' CXCR-4 in ora l cancel‘ cells We tried to screen several OSCC cell lines in order to obtain a suitable cell line model which had the cha ract eris tic of the constitutive ly expressed state of CXCR• 4 Of the several OSCC cell lines, only KOSCC-25B showed the high expression of CXCR-4 in both RT-PCR and Western blot analysis, siRNA-CXCR-4 infected subclones of KOSCC-25B(Si, 3‘ Si 1이 showed downregulation of CXCR-4 expression as expected‘ At serum-free co ndi tion‘ Si.3 s ubclone s ignif icantly decreased cell proliferations at 24 h and 48h and Si, lO subclone significant ly dec reased cell proliferations at 24 h Si ,3 clone dec reased to 67 ,4% and Si,lO clone to 65 ,5% in comparison to vector infected cells These data suggest that the downregulation of CXCR-4 expression could induce anti-rnigratory and ant i- rni g ratory effect