| ObjectiveGastric cancer is one of the most common malignant tumors in China,its prognostic bad and survival rate low.The invasion and metastasis of which is one of the most important causes related to recurrence.With the further research about gastric cancer,we now know that the invasion and metastasis of gastric cancer is a complex biological process with multiple phases and steps,in which locomotion and invasivenes are necessary for gastric cancer cells to metastasize.Invasion and metastasis of gastric cancer in molecule level is related to cell adhesion,degradation of ECM and cell movement.But up to now,these questions are still not clear.Micromolecule G proteins is an important member of signal transduction molecule,whose biological function is to regulate cytoskeletal reorgnization,body polarization,genetic transcription,cell cycle,cell adhesion,motion and migration.Rho is one of the subgroup of the small molecule G proteins super family,including Rho(RhoA,RhoB,RhoC),Rac(Rac1,Rac2,Rac3, RhoG),Cdc42(Cdc42H,G25K,TC10),Rnd(Rho/ERnd3,Rnd1/Rho1,Rnd2/Rho7),RhoD和TTE,which can regulate tumor origin and development.Recent studys showed that proteins of RhoC actively took part in regulating tumor metastasis,which called molecular switcher of tumor invasion and metastasis.But up to now,the relationship about RhoC and gastric cancer invasion and metastasis is not reported,and the correlation between RhoC and adhesion molecule ICAM-1,CD44v6,which were confirmed relating to invasion and metastasis of gastric cancer,is still not reported.So in this study,we firstly examined the expression of RhoC in gasric cancer cells MKN45,then we examined the expression of RhoC in MKN45 with different invasive and metastatic potentials and analysed the correlations between them.Thirdly,we detected the expression of RhoC,ICAM-1 and CD44v6 in gastric cancer tissues and analysed its relationship with the clinicopathological parameters.we Initially investigate whether the expression of RhoC,ICAM-1 and CD44v6 in gastric cancer tissues is related,Through this research,We hope to explore the possible role of RhoC in the invasion and metastasis of gastric cancerMethods(1) Two subpopulations with different affinity to laminin(LN) were separated from human gastric cancer cell line MKN-45 by adhesion screening in vitro,the differences in cytoskeletal morphology and the invasive and metastatic potentials both in vitro and in vivo between them were observed.Then the expressions of RhoC protein were detected by cellular immunohistochemistry,at the same time correlations between the expression of RhoC and the invasive and metastatic potentials of gastric cancer cells also were analysed.(2) we gathered 40 exairesis samples of gastric cancer tissues with different clinical stages whose clinical data were complete,without Preoperative radiotherapy and chemotherapy,all the samples were confirmed adenocarcinoma by pathological analysis after operation.we also gathered 30 samples of normal gastric tissues through exairesis or gastroscope.All the samples were stained by common pathological slice and HE tinction,and we divide them according to standardization of PTNM published by UICC in 1997.SABC immunohistochemistry were used to evaluate the expressions of RhoC,ICAM-1andCD44v6 in gastric cancer tissues and normal gastric tissues.Results(1) Two subpopulations with different affinity to laminin(LN) could be separated from human gastric cancer cell line MKN-45 by adhesion screening in vitro.The one with lower affinity possessed a more regular cytoskeletal network,fewer actin bodys and pseudopodia,but the other one with higher affinity was superior in invasive and metastatic potentials,but the other one with higher affinity was superior in proliferation activity in vitro(P＜0.05).The expression of RhoC in cells with higher affinity was more intensive than that in cells with lower affinity(P＜0.05);(2) In normal gastric mucosae,there were no expression of RhoC.The incidence of RhoC protein positivty in gastric cancer was 62.5%,significantly higher than normal gastric mucosae(P= 0.001).(3) There were no significant correlation between RhoC expression and tumor differentiation(P=0.9767) and invasion(P=0.1411),but significant correlation between RhoC expression and lymph metastasis(P=0.0136) and PTNM stage(P=0.0391);(4) There were no significant correlation between CD44v6 and ICAM—1 expression and tumor differentiation and invasion(P＞0.05),but significant correlation between their expression and lymph metastasis and TNM stage(P＜0.05);(5) Also there is a close relationship between expression of RhoC and the expression of ICAM—1(r=0.354, P=0.003).If RhoC was expressed,the sensitivity and the specificity for predicting the lymphatic metastasis of the cancer was 93.75%,62.5%respectively when any of CD44v6 and ICAM—1 was observed.Conclusions(1) Positive correlations existed between the expressive intensity of RhoC and the invasive and metastatic potentials of gastric cancer cells;(2)RhoC is a useful marker of predicting the metastatic potential of gastric cancer,The coexamination of RhoC,CD44v6 and ICAM—1 might be useful to predict lymphatic metastasis of gastric cancer and may be useful for evaluating prognosis and guiding the clinical treatment;(3) There is a close relationship between expression of RhoC and the expression of CD44v6 and ICAM—1,there may be potential effect of co accommodation between them,providing experiment evidence for the further research on RhoC and adhesion molecule.
|
PDF Full Text Request