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Research

Brain Tumor Group (Collaborative Research)

At present, we are conducting research on brain tumors from various perspectives in collaboration with the laboratory of basic sciences in Kanazawa University, as well as in the clinical classroom.

Expression and function of selective water channels (aquaporins) in Glioma

We are collaborating with the Department of Vascular and Molecular Biology (formerly Second Department of Biochemistry), Kanazawa University, to analyze the expression and function of aquaporin channels (AQPs) in glioma cells.

Water molecule H2O is distributed in all cells and migrates by diffusion, and aquaporin (AQP) is a membrane protein that is distributed in all kinds of animal and plant cells, and 13 types of AQPs (AQP0-12) have been reported to be expressed and functionally expressed in glioma cells. AQP expression is also observed in Glioma, and AQP1 and AQP4 are highly expressed in Glioma and may be involved in tumor grade (proliferation, migration, invasion and angiogenesis). We have shown that.

We are exploring the possibility of new therapeutic strategies by controlling the expression of AQP, which is universally present in all cells.

Oishi M, Munesue S, Harashima A, Nakada M, Yamamoto Y, Hayashi Y. Aquaporin 1 elicits cell motility and coordinates vascular bed formation by downregulating thrombospondin type-1 domain-containing 7A in glioblastoma. Cancer Med. Apr 6. 2020

Elucidation of the mechanism of glioma progression through extracellular vesicles

In collaboration with Professor Rikishige Hanayama’s laboratory at the Institute of Nano-Life Sciences, Kanazawa University, the researchers succeeded in elucidating the mechanism of glioma invasion and metastasis by extracellular vesicles.

Extracellular vesicles are tiny particles secreted by almost all cells in the body and contain proteins, nucleic acids and lipids specific to the secretory cells. Since the composition of extracellular vesicles differs from cell to cell and disease to disease, extracellular vesicles collected from body fluids such as blood and urine are expected to be used as biomarkers for early detection of diseases and prognosis. In addition, extracellular vesicles deliver these molecules to the surrounding cells, causing various responses, and have been shown to be involved in the development of various life phenomena and diseases.

We investigated the involvement of extracellular vesicles in the development of glioma. Malignant glioma is the most malignant of all brain tumors and has a very poor prognosis, with a mean survival time of about two years even after a combination of surgery, radiotherapy, and anticancer drug treatment. Therefore, it is desirable to elucidate the mechanism of tumor progression and to develop new treatment methods.

We found that extracellular vesicles secreted by tumors create new blood vessels by delivering the tumor-associated molecule WT1 to the cells surrounding the tumor, thus creating an environment in which the tumor can invade and metastasize easily. The research has shown that extracellular vesicles are deeply involved in the progression of glioma, and suppressing their production may inhibit the invasion and metastasis of the tumor. Furthermore, it is expected to lead to early detection of glioma, prognosis and development of new treatment methods.

Tsutsui T, Kawahara H, Kimura R, Dong Y, Jiapaer S, Sabit H, Zhang J, Yoshida T, Nakada M, Hanayama R. Glioma-derived extracellular vesicles promote tumor progression by conveying WT1. Carcinogenesis May 28, 2020

Development of new therapeutic drugs using exosomes

Exosomes are a type of extracellular vesicles that contain specific molecules and express a large number of proteins on their surface. By manipulating the expression of these surface proteins, it is thought that efficient drug delivery to target cells and information exchange is possible.

We are currently working on the development of new glioma drugs by utilizing the characteristics of the exosome.