Chemokines Expressed In MIA PaCa-2 And The Function Of CCL25/CCR9 To This Cell Line

Pancreatic cancer is one of the most malignant tumors, which has very poor prognosis. Only 10%-15% of the patients have chance to receive operation, 5%-7.5% have chance to accept complete resection. Even after resection, it has high incidence to reccur. There are several problems in the treatments of pancreatic cancer, such as it is-difficult to be diagnosed in the early time of pancreatic cancer, the development of disease is quick, it is easy to find local invasion and distal metastasis, furthermore it is not sensitive to chemotherapy and radiotherapy. Chemokines are a family of protein which can attract the white blood cells. In recent years, it is suggested that chemokines can promote tumor cells proliferation, migration, and invasion. But it is still not clear which of the chemokines play the important role during the disease.Objective(1) To chose the important chemokines and receptors associated with the invasiveness and migration in pancereatic cancer cell MIA PaCa-2 by cDNA genearray.(2) Use monoclonal antibody to block the interaction of chemokines and its receptors, observe the change of invasive and metastatic ability for the pancreatic cancer cells. From this we can know the feasibility to block the interaction of chemokines and its receptors in clinic treatment of pancreatic cancer.MethodsTo set up an orthotopic animal model for pancreatic cancer. Use cDNA genearray to find the difference of expressed chemokines and receptors between the tumor in early and late period of pancreatic cancer, and chose one chmokine and its receptor to be the further study index of immunohistochemistry, RT-PCR, real-time PCR, and Western Blot. And use MTT, flow cytometry(FCM), and transwell to find the effect of the chemokine for the pancreatic cancer cell proliferation and chemotaxis before and after the blockade of monoclonal antibody of the receptor.Results(1) We've set up the orthotopic animal model of pancreatic cancer in nude mouse.(2) By cDNA gene array, we chosed CCL25/CCR9 which is higher expressed in late period of pancreatic cancer as our further study index. By immunohistochemistry, RT-PCR, real-time PCR and Western Blot, we confirmed that in samples of late period of pancreatic cancer CCL25/CCR9 is expressed much higher.(3) CCL25 can enhance the proliferation and invasion of MIA PaCa-2 cell. By monoclonal anti-CCR9, this enhancement can be weakened evidently.ConclusionPancreatic cancer in late period has higher expression of CCL25/CCR9. CCL25 can promote MIA PaCa-2 cell proliferation, invasion and migration. If we block the interaction between CCL25 and CCR9, the proliferation, invasion and migration of MIA PaCa-2 cell can be weakened.