The Role Of L1CAM In Promoting Malignant Progression Of Breast Cancer

PurposeTo investigate the expression level of L1-cell adhesion molecule(L1CAM)in breast cancer tissues,and to study the role of L1 CAM in breast cancer proliferation,apoptosis and metastasis.At the same time,we are looking for a cationic polymer carrier with high efficiency,low toxicity,targeting and high transfection efficiency,which is expected to be applied to the research of L1 CAM.Method 1.We collected 100 patients with breast cancer who underwent surgery from the Department of Breast Surgery in Nanjing Medical University Affiliated Huai'an First Hospital,from 2008 to 2012.Breast cancer tissues and self-control normal breast tissues were obtained,and the expression level of L1 CAM was detected by immunohistochemistry.2.We detected L1 CAM expression in different breast cancer cell lines,selecting the breast cancer cell lines with high expression levels for subsequent experiments.After interfering with L1 CAM expression in breast cancer cell lines,we then use CCK-8,flow cytometry,wound healing test,transwell test and other methods to detect the effects of L1 CAM on the proliferation,apoptosis and invasion of breast cancer cells.3.A RAFT polymerization method was designed to prepare BNHEMA-b-APMA block polymer,taking 4,4'-azobis(4-cyanovaleric acid)(ACVA)as an initiating agent and 4-cyanopentanoic acid dithiobenzoate(CTP)as a chain transfer agent.RAFT polymerization was used twice to introduce BNHEMA into the cationic polymer carriers.Subsequently,the amine groups in the APMA chain were modified with methionine and the guanidinylation reagent 1-amidinopyrazole hydrochloride.Making use of the positive charges of the guanidinylation reagent and methacrylamide polymer skeleton structure,the cellular uptake efficiency of the obtained block polymer carriers was improved.Result 1.Of the 100 breast cancer patients,89(89.0%)had L1 CAM expression in breast cancer cells,while L1 CAM was not found in 11(11.0%).Among them,88% of breast cancer patients(88.0%),the expression of L1 CAM in their own contrasting breast cancer tissue cells was enhanced compared with the expression of L1 CAM in adjacent normal tissues.Statistical analysis also showed that the mean IRS of L1 CAM expression levels in self-controlled breast cancer tissues was 5.12±1.19,which was significantly higher than the mean IRS in normal breast tissues adjacent to cancer(3.08 ± 0.84).2.The expression level of L1 CAM in breast cancer cell line MCF-7 is high and stable.We then selected MCF-7 cells for subsequent experiments.It was found that the inhibition of L1 CAM expression significantly reduced the proliferation,migration and invasion of breast cancer cells,and the apoptosis ability of breast cancer cells was enhanced.3.Preparation of cationic polymer gene carriers with advantages of stability,low immunity,easy preparation,strong structure modification,targeting and unrestricted gene type,which has broad development prospects.ConclusionL1-cell adhesion molecules were highly expressed in breast cancer cells and played a critical role in cell proliferation,migration,invasion,apoptosis,and ultimately promoting the progression of breast cancer.At the same time,we designed a stable,low-immunity,easy to prepare,structurally modifyable,targeted cationic polymer gene vector,which was expected to be used in the research of breast cancer.