Cd147 Molecules In Lung Adenocarcinoma A549 Cell Biology Behavior Of The Function And Role Of Research

Malignant tumors now has become a fatal disease which threatening the humanhealth, because of its rapid growth and biologically progressive characteristics, lack ofeffective means of early diagnosis, as well as its high mortality and poor prognosis.Lung cancer tops the first tumor in case of its morbidity and mortality; in whichnon-small cell lung cancer accounting for80percent, and then the descending orderfollowed are adenocarcinoma, squamous cell carcinoma and large cell lung cancer andso on according to the pathological type. Lung adenocarcinoma is easily transferredinto hematogenous metastasis with the proportion growingly apparently in recentstudies, has also become the most common disease for women and younger patients.thus, the research on its biological characteristics has an very essential significance inclinical medicine.CD147, also known as extracellular matrix metalloproteinase inducer(EMMPRIN), derived from human lung cancer cell line LX-1, belongs to theimmunoglobulin super-family, can stimulate fibroblasts to produce matrixmetalloproteinases (MMPs). MMPs can mediate the basement membrane componentsand extracellular matrix macromolecules remodeling, promote tumor’s invasion andmetastasis and induce its angiogenesis. Mainly by keratinocytes in normal cells of thethymic epithelium, retinal pigment epithelial cells express low levels of CD147, but inmalignant tumors CD147was often higher; nowadays CDl47had been cloned in cellsof lung cancer, ovarian cancer, and liver cancer.Numerous studies have shown thatCD147is a key molecule plays an important role in various physiological orpathological processes. Although its function and the role have became popular intoday’s studies and reports, it hasn’t been verified in any medical experiments of lungcancer cells. In order to compare and analyze the function and role of CD147in thedifferent expressional levels, we constructed two types of A549cell lines: stableover-expression of CD147and interference CD147.Compared with the study whichuse only a single cell line as a control group, results of the present experiment will bemore contrast, reliable and convincing.Tumor cells experienced a rather complex multi-step process with multi-factorinvolved from proliferation to infiltration, including the degradation of basementmembrane, stoma infiltration, tumor cells out of blood vessels and the invasion of target tissues. Although the tumor has a variety of different types, it always has asignificant similar biological characteristic that promotes the growth and developmentof the tumor. High expression of CD147in tumor cell can increase the number andactivity of the MMPs, and in turn degrade the main component of basementmembrane, damage the barrier of natural organization and finally contribute to thetumor’s invasion and metastasis. At the same time, MMPs can make VEGFbiologically active which released from the ECM originally in form of non-biologicalactivity. VEGF, a specific activator of endothelial cells, can make the increasedpermeability of small blood vessels, result in leakage of plasma proteins and theformation of extra vascular fibrin gel. This not only provides a suitable environmentfor the growth of endothelial cells, but also increases the pressure within the tumororganization, impedes the delivery of nutrients, oxygen and therapeutic agents to thetumor as well as stimulates the growth of new blood vessels. Regulation of VEGFmay directly affect the formation of tumor blood vessels.Proliferation is the continuation way of the cells, tumor cells processed in thesame way. Inhibiting the proliferation is an important way of treating cancer disease.After comparing the result of the cell proliferation experiments, we found that the rateof cell proliferation in over-expression CD147group is significantly faster than othergroups; the rate of interference CD147group is the slowest. These results proved thatthe proliferation rate of lung adenocarcinoma cell will be decreased through the wayof inhibiting the activity of CD147and CD147is a fatal molecule that plays animportant role in lung adenocarcinoma cell proliferation.Invasion and metastasis are the most important biological characteristics in themalignant tumors which threatening the life of patients, and also the major obstacle tothe clinical treatment and the leading cause of death in cancer patients. Therefore,inhibition of the tumor invasion and transferred process is the most direct andeffective way for the treatment of cancer. Comparing the number of penetratedmatrigel plastic cells, high expression of CD147cells have a greater invasive ability,while the inference of CD147expression could decrease the tumor cells invasionability, in turn slow down the infiltration process. Results of the subsequent scratchtests showed that the CD147has the same role in promoting the metastasis of lungadenocarcinoma cells. Such results suggested that, inhibition the expression of CD147can reduce the ability of invasion and metastasis in the lung adenocarcinoma cells. The formation of tumor angiogenesis is essential for the primary tumor cells’proliferation and growth, and is also a necessary condition for tumors’ invasion andmetastasis runs through the whole process of tumor metastasis. We detected theexpression of VEGF in the two levels--mRNA and protein. The level of VEGFexpression increased and decreased with the respective development of CD147molecule. Results of the subsequent tube formation test are consistent with that of theexperimental results when CD147regulate the VEGF changes. Compared with thecontrol group, the number of tube formation in over-expression of CD147group wasthe most while the inference CD147group was the least. These results fully showedthat CD147could efficiently up-regulate the expression of VEGF and promote theangiogenesis. The other experiments have the same conclusions. VEGF is the mosteffective target factor of anti-angiogenic therapy, the targeted drug Bevacizumab hasbeen provided NCCN guideline for treating non-small cell lung cancer in first-line.However it has been used in clinical treatment, its clinical benefit was not satisfyingdue to its lack of effective predictor. Thus, finding a reliable benefit indicator has avery important significance. According to the characteristics of CD147over-expressed in various tumors and its regulating the expression of VEGF, manyscholars have conducted some relative researches using CD147as a predictor. In theexperiments of detecting animals’ head and neck tumors, high expression of CD147group has got the best efficacy of Bevacizumab.Speculated from our preliminary findings, CD147may play an important role inpromoting lung adenocarcinoma cell proliferation, invasion, metastasis, and increasethe expression of VEGF and thus stimulate tumor angiogenesis, it may become apotential target for tumor treatment. Our next work will pay close attention to themechanism of the CD147.