The Role And Potential Mechanism Of Heat Shock Protein-27in The Metastasis And Invasion Of Gastric Cancer

BackgroundGastric cancer is one of the most common malignancies around the world. Gastric cancerof early stage can be treated with surgery together with chemotherapy; however, patientswith late stage have a poor prognosis. Therefore, it is of major importance to find thebiomarker to predict gastric cancer and to forcast patients’ prognosis. Latest researchshowed that HSPs participated in the origin and progression of Carcinogenesis, as well asproliferation, metastasis and invasion. HSP27belongs to the sub-family of HSPs, whichalso plays an important role in tumorigenesis and acted as an indicator of poor prognosis.HSP27regulated proliferation, multipledrug-resistance and metastasis in different cancertypes, However, its relationship with metastasis of gastric cancer is still rarely reported.Therefore, this research takes this as a starting point, to study the correlation betweenexpression level of HSP27and the potential of metastasis of gastric cancer tissues and celllines, in order to find potential biomarker as an indicator of prognosis and therapyprediction. Aims1. To further analyze the protein expression level of HSP27in human gastric cancertissues and evaluate its clinicalpathological significance.2. To observe the effects of HSP27protein on the malignant behavior about metastasisof human gastric cancer cell lines.3. To investigate the underlying mechanisms of HSP27protein in metastasis andinvasion of gastric cancer.Methods1. To evaluate the expression of HSP27in gastric cancer tissues and cells.1) HSP27expression levels in gastric cancer tissues were analyzed byimmunohistochemistry and the relationship with clinicopathological featureswere analyzed statistically.2) Protein expression level of HSP27was examined by western blot in humangastric cancer cell lines with different metastatic potentials.2. To observe the effect of HSP27on gastric cancer cell metastasis.1) Transwell assay and wound healing assay were applied to analyze the effect ofHSP27on gastric cancer cells metastasis in vitro.2) In vivo tail vein metastatic assay were used for observe the effect of HSP27onmetastatic ability.3. Western blot was used to examine the expression change of some MMPs and TIMPs.Result1. Among examined118cases of gastric cancer tissues,71cases showed HSP27positive, the positive rate of this research is69%. According to statistical analysis theexpression intensity of HSP27showed positive correlation with lymph nodemetastasis, tumor size, metastasis of distant organ and pstage classification whilenegative correlation with age, gender, differentiation. Moreover, patients with negtiveHSP27expression had a better5-year survival rate those patients with positiveexpression. 2. Both western blot and qRT-PCR showed that on protein and mRNA level, gastriccancer cell lines with high potential of metastasis showed a higher expression ofHSP27that those with low metastasis potential.3. After transfected with HSP27-siRNA-mediated-lentivirus, both MKN28cell andBGC823cell showed lower HSP27expression.4. Transwell and wound-healing assays showed that, compared with negative controlgroup, si-RNA transfected cells show retarded ability in migration and invasion invitro.5. Depletion of HSP27expression inhibits gastric cancer metastasis in nude mice tailvein injection, compared with NC group.6. Western blot showed that down regulation of HSP27weaken the expression ofMMP-9in gastric cancer cells.Conclusions1. HSP27overexpressed in gastric cancer tissues, especially in cases with lymph nodemetastasis, big tumor size, distant organ metastasis, pstage classification and theexpression intensity correlated with5-year survival rate. In gastric cancer cell lines,high metastasis potential correlated with high HSP27expression.2. After down regulation of HSP27by Lentivirus-mediated-HSP27-siRNA, gastriccancer cells show retarded migration and invasion ability both in vitro and in vivo.3. HSP27participates in metastasis mechanism of gastric cancer in a multi-factor andmulti-procedure pathway. Matrix metalloproteinase-9was the downstream participant.More needs to be discovered.