Message from Director
The majority of cancer fatalities are due to metastatic recurrence. To prevent cancer metastasis, an improved understanding of the process of metastasis is highly desirable. Our primary goal is to elucidate the process of the hematogeneous metastasis, one of the metastatic modes. To achieve this goal, we have concentrated our efforts on the following two basic research projects.
Our research projects on:
1. Immune evasion strategies of cancer cells
2. Invasion processes of cancer cells
The main missions of our institute are the treatment and research of urological diseases. Our research group is conducting the basic research projects focusing on prostate cancer, bladder cancer, renal carcinoma and seminoma in collaboration with the Department of Urology, Hirosaki University Graduate School of Medicine. Our research will lead to the development of novel agents and treatment methods of those cancers in the future.
Director, Department of Cancer Immunology and Cell Biology
Shigeru Tsuboi
Publication List
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Our Research Projects
1. Immune evasion strategies of cancer cells
We innately have an ability to reject tumors, thereby limiting cancer progression and metastasis. There are two major effector lymphocytes in our tumor rejection systems. One is natural killer (NK) cells and the other one is cytotoxic T lymphocytes (CTL). In spite of those effector cell functions, cancer cells make survival in host, facilitating the metastatic spread to other organs. It has been revealed that some cancer cells acquire an ability to evade tumor rejection responses by NK cells. Several immune evasion strategies have been well-documented. Recently, we have discovered a novel immune evasion mechanism from NK immunity using cell-surface glycans.
Tumor rejection mechanism by NK cells
NK cells are innate immune cells that have the natural ability to distinguish normal cells from cancer cells and specifically kill cancer cells. In human, NK cells constitute 10-15% of peripheral blood lymphocytes. Upon encountering cancer cells in host circulation systems, NK cells eliminate the target cancer cells in several types of rejection mechanisms.
One is the NK receptor-mediated killing of cancer cells. Various receptors present on NK cells (NK receptors) are triggered during target cancer cell recognition. NK receptors are divided into two (NK activating receptors and NK inhibitory receptors). Activating receptors and inhibitory receptors induce a positive and negative cell signaling, respectively. NK cell responsiveness is controlled by a balance of these opposite signals generated from NK activating and inhibitory receptors. If the activating signaling is dominant over inhibitory signaling, NK cells recognize the target cells as "non-self" and are activated to secrete several apoptosis inducing substances such as granzyme B, perforin and cytokines, resulting in target cell killing.
Among the major NK cell activating receptors, natural killer member 2 group D (NKG2D) is the best studied receptor on its ligands. Known ligands for NKG2D are the major histocompatibility complex (MHC) class I-related molecule A/B (MICA/B) and six UL16-binding proteins (ULBP1-6). In tumor rejection responses, the MICA expression is induced and up-regulated upon cellular transformation and the engagement of NKG2D by MICA triggers the NKG2D-mediated signaling, thereby secreting the apoptosis-inducing substances to kill the target cancer cells (Fig. 1).
