Basic Study Of EPR Effect Of Tumor Microcirculation Structure

The blood vessels endothelial cells in tumors are poorly aligned with large fenestrations. Tumor vascular permeability was increased, and macromolecular drug could permeate through blood vessels into tumor. In addition, there is lack and impaired of lymphatic, and macromolecules drug remained in the tumor tissue. The phenomenon is known as the enhanced permeability and retention effect(EPR effcet). This study aims to research capillaries and capillary lymphatic system in solid tumor in mice. EPR effect is attributed to anatomical and pathophysiological alteration. Kunming mice were inoculated with S180 ascites via subcutaneous injection to establish the cancer model. The weight,volume and shape were achieved. The rules of the characteristics of solid tumor growth were observed. The expression of LYVE-1 and CD34 in tumor was detected by immunohistochemical method. To detect the expression of specific marker of lymphatic endothelial cells LYVE-1 and epithelial marker CD34 in the tissues of tumor, and to observe these capillaries and lymphatic capillaries in the edge region and central area of tumor tissues. The ultrastructural features of lymphatic capillaries of S180 sarcoma transplanted in Kunming mice were observed by transmission electron microscope(TEM)in order to analyze the ultrastructural change of lymphatic capillaries and capillaries with tumor growth. The replanting models of strain S180 were established with 100% tumor formation rate, and in accordance with the law of the tumor development. CD34 could specifically mark the capillary endothelial cells and LYVE-1 could specifically mark the capillary lymphatic endothelial cells in the tumor without tumor cells staining. The expression of LYVE-1 and CD34 in peritumoral regions was significantly higher than that in intratumoral regions. The ultrastructural changes were observed with TEM along with the development of the tumor, and the malignant degree was increased. The dissolved or damaged degree of the capillaries wall got progressively worse, and the vascular endothelial cell cracks became lager and lager. With the development of the tumor, the dissolved or damaged degree of the lymphatic capillary wall and the organelles got progressively worse, which may cause lymphatic functionality progressively worse. By detecting doxorubicin liposomal drug concentration in the tumor at different periods, we found that the EPR effect liposomal doxorubicin was presented in middle and later stages in the S180 transplanted tumor growth.