Expression Of CDCP1 In Lung Cancer And Effect Of RNA Interference On The Growth Of Cancer

The incidence rate of lung cancer is growing year by year, and it has become a great danger to mankind. For the past few years, there has a great progress in the diagnosis and treatment in lung cancer, but there is no much change in survival rate.Most of the patients with lung cancer are dead because of local recurrence and metastasis. Investigation of molecule mechanism of carcinogenesis and development are important to the early diagnosis and treatment. CUB domain-containing protein 1 is one of cell surface glycoprotein. It has been detected in stem cells or precursor cells of many tissues in vivo, for example hematopoietic stem cells/progenitor cells, nerve progenitor cells et al. CDCP1 is a cell surface transmembrane glycoprotein, the intracellular part can act with many proteins. In recent studies, some malignant tumor cells overexpress CDCP1.Phenotype and reproductive activity of malignant tumor display heterogeneity. Theory of mutations can partly explain the phenomenon. Cancer stem cell theory explains heterogeneity perfectly. Cancer stem cells are small part of tumor tissues, they have self-renewal and multi-directional differentiation characteristics. They are the roots of tumor growth, invasion and recurrence. Cancer stem cells have been separated in leukemia, brain neoplasms, breast cancer, prostate cancer, colon cancer, stomach cancer, head and neck neoplasms, lung cancer, oophoroma, melanoma, pancreatic cancer and hepatic cancer. The study of cancer stem cell surface marker is concentrated on CD133,CD44,CD34,CD38,other markers for example CD80,CD177,CD24,CD20,CD45 et al. and some CK molecules,α,βintegrin for example CK-7,C-Kit,α2β1,αvβ6 et al. These phenotypes play an important role in tumor developing and generation. With the study of cancer stem cells, cancer stem cells will be the ideal materials and target cells. Through evaluation of special cancer surface markers we can more effectively and earlier diagnose the existence of malignant tumor; we can develop new medicines targeting cancer stem cells which can radically cure tumor without killing all tumor cells.It has already been reported that using genetically engineered antibody aiming directly at CDCP1 can inhibit the growth and metabasis of tumor and the anchorage independence, moreover, promote the apoptosis of tumor cells. CDCP1 is the latent target of tumor biotherapy.RNA interference is a new method of gene silencing. It is widely used and has received important progress in tumor related gene function study. RNA interference is one of the significant gene therapy. It can suppress the expression of some genes which can inhibit the growth of tumor.Based on the domestic and abroad studies, adenocarcinoma of lung expressed CDCP1 and CDCP1 was detected in lung cancer stem cells.We used RNA interference to inhibit the expression of CDCP1 then observed the effects on the growth of tumor cells.We studied the mechanism of action on the aspect of apoptosis.On the basis of tissues, cell lines and stem cells of lung cancer, we play our emphasis on the depressive effects on the growth of lung cancer and we also studied the effect on apoptosis.(1) The expression of CDCPl in lung cancerTo approach the relationship of CDCP1 and tumorigenesis and developing of mankind lung cancer, we detected the expression of CDCP1 in adenocarcinoma, squamous carcinoma, megacell lung cancer, small cell lung cancer, normal lung tissue, benign lesion and precancerous change by the method of immunohistochemical technique. We found lung cancer expressed higher level of CDCP1 compared with normal lung tissues, benign pulmonary diseases and precancerous changes. There were significant relationship with lymphonode metabasis and recurrence. Adenocarcinoma of lung has higher level of CDCP1, while squamous carcinoma, megacell lung cancer, small cell lung cancer have lower level.By cell immunohistochemical technique, RT-PCR and Western blot,we got the same result in lung cancer cell lines. Adenocarcinoma of lung cell lines: A549 and SPC-A-1 expressed high level of CDCP1, while small cell lung cancer expressed low level. On the basis of the study of expression of CDCP1 in lung cancer,we culture lung cancer stem cells in vitro in order to approach the expression of CDCP1 in lung cancer stem cells. We detected stem cell marker CD133 by immumocytochemistry method to prove the characteristic of microsphere. We also detected the expression of CDCP1, but there were difference in expression intensity.Our study proved that the abnomal expression of CDCP1 in lung cancer was associated with tumorigenesis. The commonly used cell lines of adenocarcinoma of lung express CDCP1 and these cell lines can be used in empirical study in vitro. The result also showed that tumor stem cell expressed CDCP1.(2) Expression silencing of CDCP1 by RNAi inhibited gene expression and effected the growth of lung cancer.Expression silencing of CDCP1 by RNAi could inhibit CDCP1 gene expression. Cell multiplication was inhibited by expression silencing of CDCP1 by RNAi. In the cell population, the apoptositic cells significantly increased. And the expression of apoptosis relative protein caspase were increased.Our results showed that expression silencing of CDCP1 by RNAi could significantly effect gene expression, and it could inhibit the growth of tumor, one of the promotion apoptosis.We approved CDCP1 was mainly expressed in adenocarcinoma of lung and it was associated with the development to tumor. There was a high level in lung cancer stem cells. Expression silencing of CDCP1 by RNAi could inhibit the growth of lung cancer and promote apoptosis. The treatment targeting CDCP1 can produce a marked effect on the level of cancer stem cells.