Vascular Biology and Molecular Pathology

Blood vessels are deeply involved in the pathogenesis of cancers, heart and cerebrovascular diseases in national diseases, and due to their immense contribution to the onset and progression of diseases it is possible to treat the diseases by targeting blood vessels. Vascular endothelial cells, which line the inner walls of blood vessels, are essential targets for new cancer therapeutics and antiangiogenic drugs, since their role in angiogenesis is critical to cancer development and metastasis, . However, current antiangiogenic agents targeting blood vessels have elicited several issues. For example, injury to normal blood vessels which leads to adverse side effects and tolerance problems. Furthermore, there are no companion diagnostic agents, which makes it difficult to decide treatment timing, administration period, and select patients. Thus, the necessity of constructing new angiogenesis inhibition strategies has been fully recognized. We have isolated and cultured tumor endothelial cells (TEC) and have demonstrated that they are different from normal endothelial cells (NEC). We have also discovered and revealed phenotype of TEC.

As part of our future projects, we will conduct basic research on 1) The development of diagnosis and treatment modalities targeting TEC markers (Fig. 1), 2) Elucidation of the relationship between TECs and the cancer microenvironment (Fig. 2), 3) Elucidation of the role of TECs in drug resistance and cancer metastasis, and 4) Involvement of TEC in cancer immunity. Furthermore, additional research will be perf ormed on TECs to reveal the heterogeneity of blood vessels in different organs and pathological conditions such as metabolic and neurological diseases among others. Our lab has been collaborating with clinicians and researchers based on disease pathology to facilitate translation research. In this term’s project, we will promote such translational studies by cooperating with Dr. Harashima in Institute of Pharmaceutical Research Institute, and Dr. Tokeji in Institute of Engineering Research Institute to develop a new treatment strategy using vascular targeting nanomedicine.

Development of tumor blood vessel specific drugs

 

The relationship between TECs and the tumor microenvironment

 

Keywords：Blood vessels, Endothelial cells，cancer，angiogenesis，antiangiogenic therapy，tumor microenvironment，pathology