Professor Hiroshi Nakada

■ Area and Subject Taught: Immunochemistry
■ Research Theme(s): Cancer Cell Characteristics and Their Eﬀect on Immune Mechanisms
■ Academic Degrees: Doctor of Pharmacology, Kyoto University
■ Keywords for Research Field: Tumor Immunology, Glycobiology, Mucin

[Research Overview]

Currently, one in every two to three Japanese dies of cancer. It is said that the 21st century will be the age of the life sciences, and one of the most expected advances is the discovery of a cure for cancer. Cancer cells are foreign matter within our bodies, and it is supposed to be the job of the body's immune defense to eliminate this kind of matter. However, cancer cells use clever methods to weaken our immune reactions or even to turn our immune systems against us, allowing themselves to multiply and spread. My research aims to elucidate, at the molecular level, the mechanism by which immunological competence is reduced, to develop methods to halt this process, and to apply these methods to new treatments for cancer. The most common cancer cells are derived from epithelial cells. This type of cell generates a glycoprotein called mucin, which is secreted into the cancerous tissue and blood of the patient. It is now becoming clear that this substance acts on the immune cells (monocytes/macrophages, B cells, NK cells, dendritic cells) via a variety of receptors, inhibiting their functioning. This research is one of central post-genome issues, and we anticipate that new advances can be made by combining it with research at the genetic level.

[Notable Publications and Works in the Last Three Years]

１）Ishino, H., Kawahita, Y., Hamakuchi, M., Takeuchi, N., Tokumaga, D., Hoji, T., Wada, M., Yamamoto, A., Kadoya, M., Tsubouchi, Y., Kohno, M., Nakada, H. Expression of Tn and stalye Tn autigens in synovial tissues in rheumatoid arthritis Clin. Exp. Reumatol. in press

2) Toda, M., Hisano, R., Yurugi, H., Akita, K., Maruyama, K., Inoue, M., Adachi, T., Tsubata, T., Nakada, H. Ligation of tumor-produced mucins to CD22 dramatically impairs splenic marginal zone B cells. Biochem. J., 417: 673-683, 2009 [Feb 14, 2009]

３） Toda, M., Akita, K., Inoue, M., Taketani, S., Nakada, H. Down-modulation of B cell signal transduction by ligation of mucins to CD22. Biochem. Biophys. Res. Commun., 372: 45-50, 2008 [July 18, 2008]

Ishida, A., Ohta, M., Toda, M., Murata, T., Usui, T., Akita, K., Inoue, M., Nakada, H. Mucininduced apoptosis of monocyte-derived dendritic cells during maturation. Proteomics, 8: 3342-3349, 2008 [August, 2008]

５）Yokoigawa, N., Takeuchi, N., Toda, M., Inoue, M., Kaibori, M., Yanagida, H., Inaba, T., Tanaka, H., Ogura, T., Takada, H., Okumura, T., Kwon, A-H., Kamiyama, Y., and Nakada, H. Overproduction of PGE2 in peripheral blood monocytes of gastrointestinal cancer patients with mucins in their bloodstream. Cancer Lett., 245: 149-155,2007 [Jan 8, 2007]

６）H. Nakada ; Biological signiﬁcance of mucins produced by epithelial cancer cells. Experimental Glycoscience (eds. N. Taniguchi, A. Suzuki, Y. Ito, H. Narimatsu, T. Kawasaki and S. Hase).pp238-245. 2008, Springer.