Role of the extracellular matrix in variations of invasive pathways in lung cancers

Among the most common features of highly invasive tumors, such as lung adenocarcinomas (AD) and squamous cell carcinomas (SqCC), is the massive degradation of the extracellular matrix. The remarkable qualitative and quantitative modifications of hyaluronidases (HAases), hyaluronan synthases (HAS), E-cadherin adhesion molecules, and the transforming growth factor β (TGF-β) may favor invasion, cellular motility, and proliferation. We examined HAase proteins (Hyal), HAS, E-cadherin, and TGF-β profiles in lung AD subtypes and SqCC obtained from smokers and non-smokers. Fifty-six patients, median age 64 years, who underwent lobectomy for AD (N = 31) and SqCC (N = 25) were included in the study. HAS-1, -2 and -3, and Hyal-1 and -3 were significantly more expressed by tumor cells than normal and stroma cells (P < 0.01). When stratified according to histologic types, HAS-3 and Hyal-1 immunoreactivity was significantly increased in tumor cells of AD (P = 0.01) and stroma of SqCC (P = 0.002), respectively. Tobacco history in patients with AD was significantly associated with increased HAS-3 immunoreactivity in tumor cells (P < 0.01). Stroma cells of SqCC from non-smokers presented a significant association with HAS-3 (P < 0.01). Hyal, HAS, E-cadherin, and TGF-β modulate a different tumor-induced invasive pathway in lung AD subgroups and SqCC. HAases in resected AD and SqCC were strongly related to the prognosis. Therefore, our findings suggest that strategies aimed at preventing high HAS-3 and Hyal-1 synthesis, or local responses to low TGF-β and E-cadherin, may have a greater impact in lung cancer prognosis.

Construction of eukaryotic expression vector of human HYAL1 gene and its expression in MCF-7 and ZR-75-30 cells / 第三军医大学学报

ObjectiveTo construct the eukaryotic expression vector of human HYAL1 gene and obtain MCF-7 and ZR-75-30 cell clones expressing HYAL1 gene stably.MethodsThe cDNA encoding HYAL1 gene of human breast cancer was amplified by RT-PCR from the total RNA isolated from human MDA-MB-435S cells and inserted into pcDNA3.1/V5-His-TOPO vector.The recombinant plasmid was transferred into MCF-7 and ZR-75-30 cells.ResultsA 1332-bp DNA fragment was successfully amplified from human MDA-MB-435S cell.Restriction enzyme digestion analysis and DNA sequencing showed that HYAL1 gene was inserted into recombinant vector.RT-PCR analysis revealed that HYAL1 gene could be expressed stably in the transfected MCF-7 and ZR-75-30 and it had strong invasive potential.ConclusionThe eukaryotic expression vector of human HYAL1 gene was successfully constructed.MCF-7 and ZR-75-30 cell clones that can express HYAL1 gene were obtained and can promote the invasion.