Tohoku University · Medicine
카토 유키나리 교수의 연구실은 주로 종양 미세환경과 혈소판 상호작용을 중심으로, 특히 편평선세포막단백질(Podoplanin)과 C-type lectin-like receptor-2(CLEC-2) 간의 상호작용이 암 전이에 미치는 영향을 규명하는 데 초점을 맞추고 있습니다. 또한, 암세포에서 특이적으로 발현되는 이상점당화된 포도당산단백질을 타겟으로 한 고유의 단일클론 항체 개발을 통해 정상세포에 영향을 주지 않는 치료적 접근을 모색하고 있습니다. 특히 뇌신생물, 결장암 등 다양한 암에서의 전이 메커니즘과 그 치료적 타겟을 밝혀내는 데 기여하고 있습니다.
Figures are computed from collected data and may differ slightly.
The mucin-type sialoglycoprotein podoplanin (aggrus) is involved in tumor cell-induced platelet aggregation and tumor metastasis. C-type lectin-like receptor-2 (CLEC-2) was recently identified as an endogenous receptor of podoplanin on platelets. However, the pathophysiological importance and function of CLEC-2 have not been elucidated. Here we clarified the pathophysiological interaction between podoplanin and CLEC-2 in vitro and in vivo. Using several deletion mutants of CLEC-2 expressed as Fc
Platelets play an important role in hemostasis, thrombosis, and antimicrobial host defense and are also involved in the induction of inflammation, tissue repair, and tumor metastasis. We have previously characterized the platelet aggregation-inducing sialoglycoprotein (Aggrus/gp44) overexpressed on the surface of tumor cells. Because a platelet aggregation-neutralizing 8F11 monoclonal antibody that could specifically recognize Aggrus suppressed tumor-induced platelet aggregation, we have previou
Podoplanin (PDPN/Aggrus/T1α), a platelet aggregation-inducing mucin-like sialoglycoprotein, is highly expressed in many cancers and normal tissues. A neutralizing monoclonal antibody (mAb; NZ-1) can block the association between podoplanin and C-type lectin-like receptor-2 (CLEC-2) and inhibit podoplanin-induced cancer metastasis, but NZ-1 reacts with podoplanin-expressing normal cells such as lymphatic endothelial cells. In this study, we established a cancer-specific mAb (CasMab) against human
Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer deaths worldwide. Surgery or surgery plus radiotherapy and/or chemotherapy for patients with metastatic CRC (mCRC) were accepted as the main therapeutic strategies until the early 2000s, when targeted drugs, like cetuximab and bevacizumab, were developed. The use of targeted drugs in clinical practice has significantly increased patients' overall survival. To date, the emergence of several type
CD44 is a transmembrane glycoprotein that regulates a variety of genes related to cell-adhesion, migration, proliferation, differentiation, and survival. A large number of alternative splicing isoforms of CD44, containing various combinations of alternative exons, have been reported. CD44 standard (CD44s), which lacks variant exons, is widely expressed on the surface of most tissues and all hematopoietic cells. In contrast, CD44 variant isoforms show tissue-specific expression patterns and have
Podoplanin (PDPN) is expressed in several normal tissues including podocytes of renal glomerulus, lymphatic endothelial cells (LECs), and type I alveolar cells of lung. PDPN activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelets. Many monoclonal antibodies (mAbs) against human PDPN, mouse PDPN, rat PDPN, rabbit PDPN, and bovine PDPN have been established; antidog PDPN (dPDPN) mAbs have not been developed. Herein, we immunized mice with the recombinant pr
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