MMP2 peptide

Background: Emerging studies have demonstrated that the Forkhead transcription factor FOXO3a is closely correlated with the progression of multiple tumors. Nevertheless, the biological role and prognostic value of FOXO3a have yet to be fully elucidated in cervical carcinoma. This study was designed to determine the molecular mechanism and prognosis of FOXO3a in cervical carcinoma. Methods: The protein levels of FOXO3a were detected using immunohistochemistry and Western blotting. The relationships between FOXO3a expression and clinicopathological variables were analyzed. The biological mechanism of FOXO3a in cervical carcinoma cells (HeLa and CaSki) was investigated. We also explored the effect of FOXO3a on WNT/beta-catenin signaling with respect to its expression and function. Results: The results demonstrated that decreased FOXO3a expression was related to increased tumor stage and grade, positive lymph node metastasis, and poor survival outcome in cervical carcinoma. Survival analysis revealed that the FOXO3a level is an independent prognostic factor for cervical carcinoma patients. Furthermore, the data indicated that the downregulation of FOXO3a expression promotes cell invasion and migration, while FOXO3a overexpression exhibited the opposite effects on cervical carcinoma. In addition, FOXO3a acted as a negative regulator of the canonical WNT/beta-catenin pathway in cervical carcinoma. Moreover, overexpression of FOXO3a also inhibited the expression of MMP2 and MMP9. Conclusion: These results reveal that FOXO3a, serving as a tumor suppressor gene, could suppress cell invasion and migration via the WNT/beta-catenin signaling pathway and indicates a good prognosis in cervical carcinoma.

Background. Glioma-associated microglia/macrophages (GAMs) comprise macrophages of peripheral origin and brain-intrinsic microglia, which support tumor progression. Chemokine C-C ligand 5 (CCL5) is an inflammatory mediator produced by immune cells and is involved in tumor growth and migration in several cancers, including glioma. However, the mechanisms detailing how CCL5 facilitates glioma invasion remain largely unresolved. Methods. Glioma migration and invasion were determined by wound healing, transwell assay, and 3D mu-slide chemotaxis assay. The expression levels of CCL5, CD68, matrix metalloproteinase 2 (MMP2), phosphorylated Ca2+/calmodulin-dependent protein kinase II (p-CaMKII), p-Akt, and phosphorylated proline-rich tyrosine kinase 2 were determined by cytokine array, quantitative PCR, western blot, or immunohistochemistry. Zymography and intracellular calcium assays were used to analyze MMP2 activity and intracellular calcium levels, respectively. Results. CCL5 modulated the migratory and invasive activities of human glioma cells in association with MMP2 expression. In response to CCL5, glioma cells underwent a synchronized increase in intracellular calcium levels and p-CaMKII and p-Akt expression levels. CCL5-directed glioma invasion and increases in MMP2 were suppressed after inhibition of p-CaMKII. Glioma cells tended to migrate toward GAM-conditioned media activated by granulocyte-macrophage colony-stimulating factor (GM-CSF) in which CCL5 was abundant. This homing effect was associated with MMP2 upregulation, and could be ameliorated either by controlling intracellular and extracellular calcium levels or by CCL5 antagonism. Clinical results also revealed the associations between CCL5 and GAM activation. Conclusion. Our results suggest that modulation of glioma CaMKII may restrict the effect of CCL5 on glioma invasion and could be a potential therapeutic target for alleviating glioma growth.