Expression Of Leptin And Its Functional Receptor OB-Rb In Non-small Cell Lung Cancer And Clinicopathologic Research

Background:Lung cancer is one of the most common malignancies in the world. Non-small cell lung cancer(NSCLC) comprises about 75-80%of all lung cancers and represents a heterogeneous group of cancers,consisting mainly of squamous cell carcinoma,adenocarcinoma,adenosquamous carcinoma and large cell carcinoma subtypes.The growth and metastasis of lung carcinoma involves cell proliferation,angiogenesis,and a series of physiopathologic steps. Angiogenesis,the process of new blood vessel formation,can give adequate vascular support to sustain proliferation,survival and spread of the malignant cells.There,tumor cells gain access to lymphatic and blood vessels,followed by transportation and extravasation into distant anatomical sites,and proliferation into metastatic foci.Since tumor growth and metastasis are considered to be angiogenesis-dependent,therapeutic strategies aimed at inhibiting angiogenesis are theoretically attractive.Leptin,a product of the obese(ob) gene,is a multifunctional hormone produced predominantly by adipocytes.Leptin has been theorized to have several functions in regulating food intake and energy expenditure,inhibiting cell apoptosis,promoting proliferation and angiogenesis in both normal and tumor cells.Leptin's role as an angiogenic factor stimulated angiogenesis in both in vitro and in vivo models.Leptin enhanced vascular endothelial cell proliferation in vitro with potency similar to that of VEGF.The expression levels of leptin and leptin receptor(OB-R) have been shown to be significantly elevated in a variety of human cancers such as breast cancer,colon carcinoma,and supported its involvement in cancer development and progression.The functional leptin receptor(OB-Rb) was identified in normal human lung tissue and in lung squamous cell cancer derived cell line(SQ-5),suggesting that the lung is a peripheral site of action for leptin.Human recombinant leptin may stimulate SQ-5 cell proliferation by increasing the activity of cell proliferation-related enzymes such as MAP kinase.A rationale exists for leptin and its functional receptor OB-Rb involvement in non-small cell lung cancer(NSCLC) development,albeit its mechanisms are not thoroughly studied.Objective:This study was designed to investigate the protein and mRNA expression of leptin and its functional receptor OB-Rb in non-small cell lung cancer(NSCLC) and tumor-free lung tissues,and analyse the relationship of leptin and OB-Rb with various clinicopathological such as tumor's histological type,lymph node metastasis,TNM stage.To explore the relationship between expression of leptin and OB-Rb and oncogenesis development and clinical characteristic of lung cancer.Methods:Reverse transcription polymerasechain reaction(RT-PCR),immunohistochemical staining and western blotting were used to evaluate the mRNA and protein expression of leptin and OB-Rb in 38 NSCLC tumor tissues and 38 samples of corresponding adjacent lung tissue,and the relationship between the mRNA and protein expression of them and clinic pathological parameters was also analysized.Results:Protein positive expression of leptin and OB-Rb were detected in a significantly greater proportion of NSCLC(71.1%and 63.2%) than adjacent normal lung tissue(26.3%and 31.6%),P＜0.005 and 0.010.The expression leptin and OB-Rb was no correlated with histologic subtype,differentiation,TNM stages or lymph node metastases of NSCLC(P＞0.05).There was no relationship between leptin and OB-Rb overexpression in NSCLC(P＞0.05).It was also proved that the mRNA and protein expression level of leptin and OB-Rb in lung cancer tissue was significantly higher than that in adjacent normal lung tissue by RT-PCR and western blotting(P＜0.010).Conclusions:The up-regulation expression of leptin and OB-Rb in NSCLC suggested that leptin may be identified as a potential growth factor in the pathway of carcinogenesis and development in NSCLC.There was no directly synergetic effect between leptin and OB-Rb in the process of tumor-promoting of NSCLC. Leptin and OB-Rb may be independently involved in the pathogenesis of lung cancer.