| There are many genes change their expression form and regulate many physiological programs in tumor development. Many researchers found the microenvironment, where tumor is, is very important in tumor genesis. The tumor microenvironment contains the base-membrane around the tumor, blood vessels, lymphatic, leukocyte, lymphocyte and platelet. All of them can regulate tumor genesis and development.Genetically engineered mouse (GEM) is good model to be used in research field of human disease. Rip1-Tag2 mouse model is a classic GEM for tumor genesis. In this model the abnormal cell is spontaneous. The tumor genesis program is close to human. Additionally, this model has been studied very well, the course of diseases in this model is clear. So on the basis of this model, if we change one or two parameters, we can analyze the results simply by comparison.There have studies about the function of Slit2 and P-selectin in null mice. But the tumor planted into null mice does not exactly simulate the nature tumor. We used Slit2 over expressed/Rip1-Tag2 mice and P-selectin knockout mice as our research flat. These models are more accurate than null mouse models, from which we can get more precise comprehension about these two genes'functions in tumor genesis. Objective:In order to discover how the different genes control those elements in tumor microenvironment, and what effects on tumor occurrs and growth.Methods:Used Rip1-Tag2 mice cross-fertilized with slit2 over expressed mice or P-selectin knockout mice. Got slit2 over expressed/ Rip1-Tag2 mice and P-selectin knockout/ Rip1-Tag2 mice.We compared the tumor volume and the number of blood-pancreatic islets between slit2 over expressed/ Rip1-Tag2 mice (or P-selectin knockout/ Rip1-Tag2 mice) and Rip1-Tag2 mice. We observed the vessel, lymphatic and the leukocyte in the tumor, as well as the metastasis phenomenon, and compared the differences between these two mice.We also compared the tumor volume and number of blood- pancreatic islets between P-selectin Knock Out/ Rip1-Tag2 mice and Rip1-Tag2 mice. Besides, Observed the platelet, leukocytes and vessels in the tumor or around the pancreatic islet tumor, and compared the differences between these two mice model.Results:We found over expressed Slit2 could promote more vessel and lymphatic growth in the tumor. This made the tumor grow faster: The tumor is bigger, and blood-pancreatic islets are more than normal Rip1-Tag2 mice. While there are 25% of Slit2/Rip1-tag2 mice found having metastasis carcinoma ofβpancreatic islet cell tumor.In P-selectin Knock Out/ Rip1-Tag2 mice the tumor is smaller than that in normal Rip1-Tag2 mice, and the tumor's growth is slower. In the 10 weeks'P-selectin Knock Out/Rip1-Tag2 mice the number of blood-pancreatic islets is less than normal Rip1-Tag2 mice. There is no platelet dollop aroundβpancreatic islet cell tumor in P-selectin Knock Out/Rip1-Tag2, but in Rip1-Tag2 mice we can find platelet dollop aroundβpancreatic islet cell tumor. The angiogenesis of tumor vessle in P-selectin Knock Out/ Rip1-Tag2 is less than Rip1-Tag2 mice. The leukocytes'level in blood is the same in these two mice, but the number of leukocytes, which are around theβpancreatic islet cell tumor, is less than that in normal Rip1-Tag2 mice.Conclusion:Slit2 and P-selectin are important genes that can regulate the tumor microenvironment.Slit2 gene can regulate angiogenesis and lympho-genesis. Over-expressed Slit2 can make more vessels grow in tumor, and this can facilitate tumor growth. It also can up-regulate lympho-genesis, then give tumor cell a pathway to metastasis.P-selectin can modulate platelet to adhere to tumor cell, which has effect on tumor angiogenesis. Knocking out P-selectin gene can make platelet dollops vanish in tumor or in the tissues around the tumor. That weakens the angiogenesis, and tumor growth.
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