Expression And Clinical Significance Of EphB4 In Non-small Cell Lung Cancer

Primary bronchogenic carcinoma or lung cancer is one of the severemalignant tumor affecting healthy and life. Pulmonary cancer have beencatalogued into SCLC and NSCLC according to pathology. Classify NSCLCinto squamous cell lung carcinoma (SCC), adenocarcinoma, large cell lungcarcinoma(LCLC) and adenocaroumatous, carcinoid, et al. Because of theinsensitiveness to radiation therapy and chemotherapeutics and with itsincidence and mortality rate increasing year by year, NSCLC has caught moreand more attention in the research about the prognosis, genesis, development,diagnosis and treatment.Eph(Erythropoietin producing hepatoma)are the largest family of receptortyrosine kinase. The Eph family have been divided into A and B subgroupaccording to the homology of extracellular structure field , structure and theaffinity for ligand. Studies have indicated that EphB4 have drawn increasingattention as important components of signal transduction pathways. EphB4 playkey roles in diverse biological processes such as embryonic development,formation of neuronal network, guidance of cell migration and axon pathfinding,and vascular formation. Since the EphB4 was identified as receptor,greatprogress has been made in the study of its structure and various functions,especially it is closely related with tumor's occurrence and development andattracted many researchers. EphB4 receptors might also play pivotal role inneoangiogenesis. EphB4 accelerate vascular endothelial cell budding, migration,proliferation. The detune of EphB4 can promote cell unrestricted growth andinduce the process of malignant transformation and tumor's formation. Someresearches indicate the level of EphB4 expression correlates with the degree oftumor malignancy . EphB4 is closely correlated with histological grade andclinical stages of lung cancer。For the present,the relations between EphB4 andlung cancer is in the stage of data's apprehend and accumulation,especially therelations between EphB4 and NSCLC is not reported,researches is in greatdemand.Despite the accumulating evidence linking them to cancer, very little isknown about how the EphB4 receptors contribute to the oncogenic process.Following are the possible mechanisms that are being studied:1. Altered extracelllular matrix adhesionEphB4 can activate the expression of MMPs-2. MMPs-9,the two factorsare of matrix metalloproteinase production. Increased degradation ofextracellular matrix has been suggested be the result of the higher expressedEphB4, which may confer a metastasis advantage on tumor cells by a abatementin cellular adhesion to the extracellular matrix.2. Enhancing angiogenesis of the tumor cellsStudies found that EphB4 is related to tumor angiogenesis as modulates theexpression of VEGF. Examination of the tumors revealed that EphB4 isexpressed in the vein endothelial cells of primarily embryogenesis. EphB4 is thebest tumor label at this stage.3. Enhancing proliferation and differentiation of the tumor cells, increasedinvasiveness and migration of tumor cells has been suggested to be the result ofthe interaction among EphB4,E-cadherin and integrin.In the experiment, immunohistochemical technique were adopted todetected the expression of EphB4 in specimen of NSCLC, normal pulmonarytissue. The results showed that the positive staining of EphB4 in specimen wasyellow, mainly localized in cellular membrane and cellular plasma and showedobvious diffusibility fashion. We found that immunostaining of EphB4 insquamous carcinoma, adenocarcinoma was on different degree. The expressionof EphB4 in normal pulmonary tissue was almost negative, few was weaklypositive, which were significantly lower than those in NSCLC, (P<0.01). Therewas a positive difference between squamous carcinoma and adenocarcinoma,but it is no statistical significance. The positive rations and levels of expressionsof EphB4 were closely related to differentiations and clinical stages (p<0.05),but not to histological classification, age, sex and lymph node metastasis(p>0.05).On conclusion: EphB4 maybe play a key role in carcinogenesis andprogression of NSCLC. The study on the biology function and the pathogenesisof EphB4 in NSCLC may offer a new way for the treatment of NSCLC.