| Background and aimCurrently, lung cancer is the highest morbidity and mortality ofmalignant tumor worldwide, particularly non-small cell lung cancer(NSCLC) accounts for about85%of the total incidence of lung cancer,and70-80%of lung cancer has been found in the late stage. It is wellknown that different histologic classification of lung cancer may resultin significant differences on the time and speed of invasion andmetastasis. The invasion and metastasis play a vital role in theprogression and prognosis of lung cancer and they are also the maincauses of death and the main bottlenecks of treatment failure.Therefore,blocking and controlling tumor invasion and metastasis are consideredas different issue in the worldwide, for which all scholars have beenexploring.Some studies indicate that the tumor invasion and metastasis are theimportant biological characteristics, however, its molecular mechanismis quite complicated, including lack of tumor cells and intercellularadhesion molecules, extracellular matrix of invasion, tumor angiogenesisand the vascular and lymphatic spread.Integrin is one kind oftransmembrane receptors of extracellular matrix and adhesion molecules,which is vital in promoting proliferation, invasion and metastasis oftumor cells.Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases and capable of degrading all kinds of extracellularmatrix proteins.MMPs are also the earliest discovered to play a majorrole on cell behaviors such as cell proliferation, migration(adhesion/dispersion).VCAM-1is a cell adhesion molecule andupregulation of VCAM-1in endothelial cells by cytokines occurs as aresult of increased gene transcription (e.g., in response to Tumornecrosis factor-alpha (TNF-α) and Interleukin-1(IL-1)).It is quiteimportant in regulating tumor angiogenesis aspects and until now thereis no report in its expression in lung tissue.This study will furtherconfirm the expression of tumor related invasion and metastasisbiomarker using molecular biology techniques in clinical level. We willalso further elucidate the possible mechanism of invasion and metastasisin different lung cancer by comparing the expression of vascularadhesion molecule in the serum of health people and NSCLC patients,the expression of vascular adhesion molecule,integrin and matrixmetalloproteinases in the lung cancer tissue and paraneoplastic tissue ofNSCLC patients, which will provide reliable biomarker in predictingoccurrence of invasion and metastasis of lung cancer and provide newperspectives in stoping and controlling invasion and metastasis of lungcancer.Methods72lung tissue of NSCLC(Ⅰ+Ⅱstage37patients，Ⅲ35patients)are from Thoracic Surgery department of the second hospital of JilinUniversity and Central Hospital of SiPing from October2010toDecember2013.All the paitients are accorded with standard of2010NCCN guidelines and confirmed without any treatment. To measure theprotein level of LFA-1、ICAM-1and VCAM-1in the serum usingenzyme linked immunosorbent assay(ELISA）.To identify the location ofexpression and measure the expression of vascular adhesion molecule （LFA-1、ICAM-1、VCAM-1、CD34and CD105）,integrin（β1、β2、β3、α5β1andαvβ3） and matrix metalloproteinases（MMP-2and MMP-9）using Immunohistochemistry(IHC）.To measure the proteinlevel of integrin α5β1andαvβ3using Western Blot（Such researchhas not yet been reported）.ResultThe protein levels of LFA-1、ICAM-1and VCAM-1in the serum ofNSCLC patients are higher than those in healthy people（p＜0.05) andthe protein levels are closely related with NSCLC staging(p <0.01)andlymph node metastasis(p <0.01).Integrin β1、β2、β3、α5β1and αvβ3are highly expressedin cancer nests and around the cancer nests in slides of patients withsquamous cell carcinoma;they are highly expressed in cancer nests andaround the cancer nests and moderate expressed in interstitium in slidesof patients with lung adenocarcinoma.The expression of CD34and CD105in lung cancer tissue aresignificantly higher than those in normal lung tissue of NSCLC patients（p<0.0001）.The expression of CD105are closely related with NSCLCstaging(p <0.01)and lymph node metastasis(p <0.01) and the expressionof CD34are only related with lymph node metastasis(p <0.05).The expression of MMP-2and MMP-9in lung cancer tissue aresignificantly higher than those in normal lung tissue of NSCLC patients（p<0.0001） and the expression of MMPs are only related with lymphnode metastasis(p <0.05).This study will for the first time confrim the expression of integrinβ1、β2、β3、α5β1and αvβ3in lung cancer tissue are significantlyhigher than those in normal lung tissue of NSCLC patients（p<0.0001）,and the protein levels of β1、β3、α5β1and αvβ3are closely related with NSCLC staging(p <0.01)and lymph node metastasis(p <0.01).Conclusion1.High level expressions of LFA-1,ICAM-1and VCAM-1in theserum of NSCLC patients provide reliable molecular markers andpotential therapeutic targets to this kind of tumor patients.2.CD105is a specific marker of newborn vessel in NSCLC.3.The expressions of MMP-2and MMP-9are closely related to theprogression and metastasis of tumor, however they express in differentplaces in squamous cell carcinoma and adenocarcinoma, thus detectionof the expression of MMP-2andMMP-9in lung cancer is helpful inpredicting type, prognosis of lung cancer and guided the postoperativemultimodality therapy for lung cancer.4.Integrins β1,β3,α5β1andαvβ3are necessary for development,invasion and metastasis of NSCLC, the expressions of these integrins arehigher in NSCLCⅠ+Ⅱstage,Ⅲ stage and lymphatic metastasis tissue,indicating that it is very important for clinical significance to understandand evaluate the biologic behavior of cancer correctly.5.The above markers in squamous carcinoma and adenocarcinomatissues high expression level in the place of difference, also furtherconfirmed that lung adenocarcinoma cancer cell invasion force strong,the biological characteristics of transfer occurs early, suggest we shouldmake the expression level in markers of the corresponding treatment,assessment of prognosis, there may be a good clinical applicationprospects. |
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