Effect Of Moesin On Perineural Invasion Of Pancreatic Cancer And The Relationship Between Moesin And Pain Of Patients With Pancreatic Cancer

Background:Pancreatic carcinoma(PAC) is common malignant neoplasms ofdigestive system tumors.Perineural invasion is one of the important features forpatients with pancreatic carcinoma,and it thus cause the difficulity in curativeresection,high local recurrence and abdominal pain.Perineural invasion has becomethe research emphasis and focus on pancreatic carcinoma.The"seed and soil"theoryforwarded by Peget in 1889 and"machine and atomy"theory forwarded by Ewing in1929 had almost emphasized tumor cell' s progressiveness and invasion of itself,passive adaptability to tissue microenviroment,tissue and organ' s anatomicalfactors abouts tumor metastasis and ignored the active contributions of organism.Atpresent,through more than 100 year' s research,plentiful and substantial outcomeshave been made in the many levels and fields such as oncogene,biomacromolecule,subcell,cell,mesenchyma microenviroment and so on.On this basis,the modemtumor metastasis theory is formed gradually that tumor metastasis is a multisteps andsequential pathological process and emphasizes the balance between numerousmetastasis and antimetastasis factors,active plasticity and specificity of host targetorgan microenviroment and the whole and/or local immunity of the host.It wasbelieved that the tumor invasion appeared to follow the plane of least resistance of theperineural space,but recent reaearch shows that some molecules on the surface ofcancer cells may have effects on the progression of tumor perineural invasion.It isnecessary,therefore,to investigate the molecular mechanisms in patients withperineural invasion.Actin cytoskeleton reorganization is reportedly regulated byezrir/radixir/moesin(ERM) family.Moesin,one member of ERM family,mainlylocalizes on membrane structures such as microvillus or lamellipodia which are richin actin fibers.The functions of moesin proteins are regulated by its conformationalcharges:the intramolecular interaction between the N-and C-terminal domains of moesin protein charges masks several binding sites,leading to a dormant protein.When stimulated by extracellular signals,moesin protein changes its conformationand is activated as the bridge molecule crosslinking the actin with plasma membraneand initiating the reorganization of actin cytosleleton.In this manner,it regulates theprocess of cell growth and migration.Recently it has been reported that moesinprotein play important roles in several tumor development and metastasis.However,to the best of our knowledge,till now there is no research focused on the relevancebetween moesin protein and pancreatic carcinoma,in particular,the role andmechanism of moesin protein on pancreatic carcinoma metastasis.Objective:To study the moesin protein's effects on the mechanism of pancreaticcarcinoma perineural invasion from operation tissue specimens.And to explore therelationship between moesin protein and the pain of the patients with pancreaticcarcinoma.Our study may provide in the future the novel therapeutic tools for thetreatment of PAC patients.Methods:(1) Expression and distribution of moesin,β-NGF and MMP-7 were detected inopration tissue specimens of pancreatic carcinoma with immunohistochemistry,RT-PCR,Real-time PCR and ELISA.The relations of moesin withβ-NGF andMMP-7 were analyzed.(2) Exploration the relationship between moesin,β-NGF and MMP-7 and thepain of the patients with pancreatic carcinoma.(3) All data were processed by SPSS version 15.0 analysis software.Results:(1) By immunohistochemistry,the expression of moesin,β-NGF and MMP-7 inthe well-,medium-and poor-differentiated PAC groups lie in the cytoplasm of tumorcell,higher than normal group (p＜0.05).The radio of PNI found was 54.55%.β-NGFand MMP-7 were correlated with perineural invasiveness.(2) By RT-PCR,real-time PCR and ELISA,we found that moesin,β-NGF andMMP-7 expression of PAC samples were higher than the other.There was great significantly difference between two groups.The result by molecular biologytechnology was correlated with it by immunohistochemistry.(3) We found that moesin,β-NGF and MMP-7 expression of in patients withpain were higher than those who without pain.Moesin,β-NGF and MMP-7 werecorrelated with perineural invasiveness.Conclusions:(1) Expression's change of moesin,β-NGF and MMP-7 may induce the formof PAC.They may play an important role on perineural invasion of human pancreaticcarcinoma.(2) Moesin,β-NGF and MMP-7 expression have something to do with pain ofPAC patients.