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https://www.readbyqxmd.com/read/28385772/clec-2-podoplanin-and-thromboinflammation
#1
Katsue Suzuki-Inoue
No abstract text is available yet for this article.
April 6, 2017: Blood
https://www.readbyqxmd.com/read/28332312/antitumor-activity-of-chlpmab-2-a-human-mouse-chimeric-cancer-specific-antihuman-podoplanin-antibody-via-antibody-dependent-cellular-cytotoxicity
#2
Mika K Kaneko, Shinji Yamada, Takuro Nakamura, Shinji Abe, Yasuhiko Nishioka, Akiko Kunita, Masashi Fukayama, Yuki Fujii, Satoshi Ogasawara, Yukinari Kato
Human podoplanin (hPDPN), a platelet aggregation-inducing transmembrane glycoprotein, is expressed in different types of tumors, and it binds to C-type lectin-like receptor 2 (CLEC-2). The overexpression of hPDPN is involved in invasion and metastasis. Anti-hPDPN monoclonal antibodies (mAbs) such as NZ-1 have shown antitumor and antimetastatic activities by binding to the platelet aggregation-stimulating (PLAG) domain of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-2, using the cancer-specific mAb (CasMab) technology...
April 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28296036/targeting-of-c-type-lectin-like-receptor%C3%A2-2-or-p2y12-for-the-prevention-of-platelet-activation-by-immunotherapeutic-cpg-oligodeoxynucleotides
#3
C Delierneux, N Donis, L Servais, O Wéra, C Lecut, M Vandereyken, L Musumeci, S Rahmouni, J Schneider, J A Eble, P Lancellotti, C Oury
Essentials CpG oligodeoxynucleotide (ODN) immuotherapeutics cause undesired platelet activating effects. It is crucial to understand the mechanisms of these effects to identify protective strategies. CpG ODN-induced platelet activation depends on C-type lectin-like receptor 2 (CLEC-2) and P2Y12. Targeting CLEC-2 or P2Y12 fully prevents CpG ODN-induced platelet activation and thrombosis. SUMMARY: Background Synthetic phosphorothioate-modified CpG oligodeoxynucleotides (ODNs) show potent immunostimulatory properties that are widely exploited in clinical trials of anticancer treatment...
March 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28294559/the-platelet-activating-receptor-c-type-lectin-receptor-2-plays-an-essential-role-in-liver-regeneration-after-partial-hepatectomy-in-mice
#4
H Kono, H Fujii, K Suzuki-Inoue, O Inoue, S Furuya, K Hirayama, Y Akazawa, Y Nakata, C Sun, N Tsukiji, T Shirai, Y Ozaki
Essentials Regeneration role of C-type lectin receptor-2 (CLEC-2) after 70% hepatectomy (HPx) was investigated. Wild-type or CLEC-2 deleted from platelets of chimeric mice (flKO) underwent HPx. The liver/body weight ratio was significantly lower in the flKO than in the wild-type. CLEC-2 plays an essential role in liver regeneration after HPx. SUMMARY: Background and aim The aim of the present study was to investigate the role of C-type lectin receptor (CLEC)-2 in liver regeneration following partial liver resection in mice...
March 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28157429/chimeric-anti-human-podoplanin-antibody-nz-12-of-lambda-light-chain-exerts-higher-antibody-dependent-cellular-cytotoxicity-and-complement-dependent-cytotoxicity-compared-with-nz-8-of-kappa-light-chain
#5
Mika K Kaneko, Shinji Abe, Satoshi Ogasawara, Yuki Fujii, Shinji Yamada, Takeshi Murata, Hiroaki Uchida, Hideaki Tahara, Yasuhiko Nishioka, Yukinari Kato
Podoplanin (PDPN), a type I transmembrane 36-kDa glycoprotein, is expressed not only in normal cells, such as renal epithelial cells (podocytes), lymphatic endothelial cells, and pulmonary type I alveolar cells, but also in cancer cells, including brain tumors and lung squamous cell carcinomas. Podoplanin activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelets, and the podoplanin/CLEC-2 interaction facilitates blood/lymphatic vessel separation. We previously produced neutralizing anti-human podoplanin monoclonal antibody (mAb), clone NZ-1 (rat IgG2a, lambda), which neutralizes the podoplanin/CLEC-2 interaction and inhibits platelet aggregation and cancer metastasis...
February 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28104688/mice-with-a-deficiency-in-clec-2-are-protected-against-deep-vein-thrombosis
#6
Holly Payne, Tatyana Ponomaryov, Steve P Watson, Alexander Brill
Deep vein thrombosis (DVT) with its major complication, pulmonary embolism, is a global health problem. Mechanisms of DVT remain incompletely understood. Platelets play a role in DVT, but the impact of specific platelet receptors remains unclear. Platelet C-type lectin-like receptor 2 (CLEC-2) is known to maintain the physiological state of blood vasculature under inflammatory conditions. DVT is a thromboinflammatory disorder developing largely as sterile inflammation in the vessel wall. We hypothesized therefore that CLEC-2 might play a role in DVT...
April 6, 2017: Blood
https://www.readbyqxmd.com/read/28101903/development-and-characterization-of-anti-glycopeptide-monoclonal-antibodies-against-human-podoplanin-using-glycan-deficient-cell-lines-generated-by-crispr-cas9-and-talen
#7
Mika K Kaneko, Takuro Nakamura, Ryusuke Honma, Satoshi Ogasawara, Yuki Fujii, Shinji Abe, Michiaki Takagi, Hiroyuki Harada, Hiroyoshi Suzuki, Yasuhiko Nishioka, Yukinari Kato
Human podoplanin (hPDPN), which binds to C-type lectin-like receptor-2 (CLEC-2), is involved in platelet aggregation and cancer metastasis. The expression of hPDPN in cancer cells or cancer-associated fibroblasts indicates poor prognosis. Human lymphatic endothelial cells, lung-type I alveolar cells, and renal glomerular epithelial cells express hPDPN. Although numerous monoclonal antibodies (mAbs) against hPDPN are available, they recognize peptide epitopes of hPDPN. Here, we generated a novel anti-hPDPN mAb, LpMab-21...
February 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28028907/c-type-lectin-like-receptor-2-promotes-hematogenous-tumor-metastasis-and-prothrombotic-state-in-tumor-bearing-mice
#8
T Shirai, O Inoue, S Tamura, N Tsukiji, T Sasaki, H Endo, K Satoh, M Osada, H Sato-Uchida, H Fujii, Y Ozaki, K Suzuki-Inoue
Essentials The role of C-type lectin-like receptor-2 (CLEC-2) in cancer progression is unclear. CLEC-2-depleted mouse model is generated by using a rat anti-mouse CLEC-2 monoclonal antibody. CLEC-2 depletion inhibits hematogenous tumor metastasis of podoplanin-expressing B16F10 cells. CLEC-2 depletion prolongs cancer survival by suppressing thrombosis and inflammation. SUMMARY: Background C-type lectin-like receptor 2 (CLEC-2) is a platelet activation receptor of sialoglycoprotein podoplanin, which is expressed on the surface of certain types of tumor cells...
March 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27960039/physiologic-and-pathophysiologic-roles-of-interaction-between-c-type-lectin-like-receptor-2-and-podoplanin-partners-from-in-utero-to-adulthood
#9
REVIEW
K Suzuki-Inoue, M Osada, Y Ozaki
A platelet activation receptor, C-type lectin-like receptor 2 (CLEC-2), has been identified as a receptor for a platelet-activating snake venom, rhodocytin. CLEC-2 protein is highly expressed in platelets/megakaryocytes, and at lower levels in liver Kupffer cells. Recently, podoplanin has been revealed as an endogenous ligand for CLEC-2. Podoplanin is expressed in certain types of tumor cells, fibroblastic reticular cells (FRCs) in lymph nodes, kidney podocytes, and lymphatic endothelial cells, but not in vascular endothelial cells...
February 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27766053/new-horizon-in-platelet-function-with-special-reference-to-a-recently-found-molecule-clec-2
#10
REVIEW
Yukio Ozaki, Shogo Tamura, Katsue Suzuki-Inoue
Platelets play a key role in the pathophysiological processes of hemostasis and thrombus formation. However, platelet functions beyond thrombosis and hemostasis have been increasingly identified in recent years. A large body of evidence now exists which suggests that platelets also play a key role in inflammation, immunity, malignancy, and furthermore in organ development and regeneration, such as the liver. We have recently identified CLEC-2 on the platelet membrane, which induces intracellular activation signals upon interaction of a snake venom, rhodocytin...
2016: Thrombosis Journal
https://www.readbyqxmd.com/read/27766044/anti-thrombotic-agents-derived-from-snake-venom-proteins
#11
REVIEW
Tur-Fu Huang, Chun-Chieh Hsu, Yu-Ju Kuo
Snake venoms affect blood coagulation and platelet function in a complex manner. However, two classes of venom proteins, snaclecs and disintegrins have been shown to specifically target receptors including GPIb, α2β1, GPVI, CLEC-2 and integrins αIIbβ3, αvβ3, α5β1 expressed on platelets, endothelial cells, phagocytes, tumor cells, thus affecting cell-matrices and cell-cell interactions. Here, we focus on disintegrins, a class of low molecular mass Arg-Gly-Asp(RGD)/Lys-Gly-Asp(KGD)-containing, cysteine-rich polypeptide derived from various viper snake venoms...
2016: Thrombosis Journal
https://www.readbyqxmd.com/read/27564251/lpmab-19-recognizes-sialylated-o-glycan-on-thr76-of-human-podoplanin
#12
Satoshi Ogasawara, Mika K Kaneko, Yukinari Kato
Human podoplanin (hPDPN) is expressed in lymphatic vessels, pulmonary type-I alveolar cells, and renal glomerulus. The hPDPN/C-type lectin-like receptor-2 (CLEC-2) interaction is involved in platelet aggregation and cancer metastasis. High expression of hPDPN in cancer cells or cancer-associated fibroblasts (CAFs) leads to a poor prognosis for cancer patients. In our previous research, we reported on several anti-hPDPN monoclonal antibodies (mAbs), including LpMab-2, LpMab-3, LpMab-7, LpMab-9, LpMab-12, LpMab-13, and LpMab-17 of mouse IgG1 subclass, which were produced using CasMab technology...
August 26, 2016: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/27564117/high-clec-2-expression-associates-with-unfavorable-postoperative-prognosis-of-patients-with-clear-cell-renal-cell-carcinoma
#13
Ying Xiong, Li Liu, Yu Xia, Jiajun Wang, Wei Xi, Qi Bai, Yang Qu, Qilai Long, Jiejie Xu, Jianming Guo
We enrolled a total of 277 patients who received nephrectomy due to clear cell renal cell carcinoma (ccRCC) in Zhongshan Hospital from Jan 2005 to Jun 2007. Immunohistochemistry was performed to evaluate the impact of CLEC-2 positive cell infiltration on the overall survival (OS) and recurrence-free survival (RFS) of patients with ccRCC. Kaplan-Meier analysis showed that high CLEC-2 positive cell infiltration in tumor tissue indicated poorer OS and RFS (OS, p < 0.001; RFS, p = 0.002). High CLEC-2 positive cell infiltration is also an independent risk factor for OS and RFS in multivariate analyses (OS, p = 0...
September 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27443248/e3-ubiquitin-ligase-chip-interacts-with-c-type-lectin-like-receptor-clec-2-and-promotes-its-ubiquitin-proteasome-degradation
#14
Miaomiao Shao, Lili Li, Shushu Song, Weicheng Wu, Peike Peng, Caiting Yang, Mingming Zhang, Fangfang Duan, Dongwei Jia, Jie Zhang, Hao Wu, Ran Zhao, Lan Wang, Yuanyuan Ruan, Jianxin Gu
C-type lectin-like receptor 2 (CLEC-2) was originally identified as a member of non-classical C-type lectin-like receptors in platelets and immune cells. Activation of CLEC-2 is involved in thrombus formation, lymphatic/blood vessel separation, platelet-mediated tumor metastasis and immune response. Nevertheless, the regulation of CLEC-2 expression is little understood. In this study, we identified that the C terminus of Hsc70-interacting protein (CHIP) interacted with CLEC-2 by mass spectrometry analysis, and CHIP decreased the protein expression of CLEC-2 through lysine-48-linked ubiquitination and proteasomal degradation...
October 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27385789/lymphovenous-hemostasis-and-the-role-of-platelets-in-regulating-lymphatic-flow-and-lymphatic-vessel-maturation
#15
REVIEW
John D Welsh, Mark L Kahn, Daniel T Sweet
Aside from the established role for platelets in regulating hemostasis and thrombosis, recent research has revealed a discrete role for platelets in the separation of the blood and lymphatic vascular systems. Platelets are activated by interaction with lymphatic endothelial cells at the lymphovenous junction, the site in the body where the lymphatic system drains into the blood vascular system, resulting in a platelet plug that, with the lymphovenous valve, prevents blood from entering the lymphatic circulation...
September 1, 2016: Blood
https://www.readbyqxmd.com/read/27380308/specific-detection-of-dog-podoplanin-expressed-in-renal-glomerulus-by-a-novel-monoclonal-antibody-pmab-38-in-immunohistochemistry
#16
Ryusuke Honma, Mika K Kaneko, Satoshi Ogasawara, Yuki Fujii, Satoru Konnai, Michiaki Takagi, Yukinari Kato
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 proteins of dPDPN and developed anti-dPDPN mAbs...
August 2016: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/27328060/establishment-of-mouse-monoclonal-antibody-lpmab-13-against-human-podoplanin
#17
Satoshi Ogasawara, Mika K Kaneko, Ryusuke Honma, Hiroharu Oki, Yuki Fujii, Michiaki Takagi, Hiroyoshi Suzuki, Yukinari Kato
Podoplanin (PDPN)/Aggrus is a type-I transmembrane sialoglycoprotein, which possesses a platelet aggregation-stimulating (PLAG) domain. The O-glycosylation on Thr52 of human PDPN (hPDPN) is critical for the interaction of hPDPN with C-type lectin-like receptor-2 (CLEC-2), resulting in platelet aggregation. Many anti-hPDPN monoclonal antibodies (MAbs) against PLAG domains and non-PLAG domains have been established; however, mouse anti-PLAG2/3 MAb, the epitope of which is consistent with rat anti-PLAG2/3 MAb NZ-1, has not been established...
June 2016: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/27267652/pmab-44-detects-bovine-podoplanin-in-immunohistochemistry
#18
Ryusuke Honma, Satoshi Ogasawara, Mika K Kaneko, Yuki Fujii, Hiroharu Oki, Takuro Nakamura, Michiaki Takagi, Satoru Konnai, Yukinari Kato
Podoplanin (PDPN)/Aggrus is a type I transmembrane O-glycoprotein, which is expressed in several normal tissues including podocytes of kidney and lymphatic endothelial cells. PDPN activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelet; however, only bovine PDPN (bovPDPN) does not possess the platelet-aggregating activity. Although many monoclonal antibodies (mAbs) against human PDPN, mouse PDPN, rat PDPN, and rabbit PDPN have been established, anti-bovPDPN mAbs have not been developed...
June 7, 2016: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/27148766/establishment-of-mouse-monoclonal-antibody-lpmab-13-against-human-podoplanin
#19
Satoshi Ogasawara, Mika K Kaneko, Ryusuke Honma, Hiroharu Oki, Yuki Fujii, Michiaki Takagi, Hiroyoshi Suzuki, Yukinari Kato
Podoplanin (PDPN)/Aggrus is a type-I transmembrane sialoglycoprotein, which possesses a platelet aggregation-stimulating (PLAG) domain. The O-glycosylation on Thr52 of human PDPN (hPDPN) is critical for the interaction of hPDPN with C-type lectin-like receptor-2 (CLEC-2), resulting in platelet aggregation. Many anti-hPDPN monoclonal antibodies (MAbs) against PLAG domains and non-PLAG domains have been established; however, mouse anti-PLAG2/3 MAb, the epitope of which is consistent with rat anti-PLAG2/3 MAb NZ-1, has not been established...
May 5, 2016: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/27034419/clec-2-and-podoplanin-partners-again
#20
COMMENT
Jianxin Fu, Lijun Xia
In this issue of Blood, Tamura et al reveal a novel function for podoplanin on periarteriolar stromal cells in the bone marrow: promoting megakaryocyte growth and proplatelet formation by interaction with C-type lectin-like receptor 2 (CLEC-2).
March 31, 2016: Blood
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