Conservation of a platelet activating domain of Aggrus/podoplanin as a platelet aggregation-inducing factor

Kaneko, Mika K.; Kato, Yoshinori; Kitano, Takashi; Osawa, Motoki

doi:10.1016/j.gene.2006.04.023

Cited by 122 publications

(93 citation statements)

References 25 publications

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“…Alternatively, there may be additional CLEC-2 binding sites on Pdpn. For instance, the ectodomain of Pdpn comprises not only one PLAG domain, but three tandem repeats, and the role of PLAG-2 and PLAG-3 has not been fully elucidated (34). Moreover, there are also reports indicating that the C-terminal region of Pdpn is necessary for its strong interaction with CLEC-2 (35).…”

Section: Mpdpnt34a-fc As An Improved Lymphangiogenesis Inhibitormentioning

confidence: 99%

Mutation of Threonine 34 in Mouse Podoplanin-Fc Reduces CLEC-2 Binding and Toxicity in Vivo While Retaining Anti-lymphangiogenic Activity

Bianchi

Fischer

Yuen

et al. 2014

Journal of Biological Chemistry

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Background: Podoplanin-Fc inhibits lymphangiogenesis, but also causes a bleeding disorder by binding to CLEC-2 expressed on platelets. Results: Mutation of threonine 34 in mouse Pdpn-Fc reduces 30-fold the binding to CLEC-2 and does not hamper its antilymphangiogenic activity. Conclusion: PdpnT34A-Fc is an active lymphangiogenesis inhibitor with a better tolerability. Significance: Mutagenesis of Pdpn-Fc is a valid approach to improve this tool for anti-lymphangiogenic therapy.

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Section: Mpdpnt34a-fc As An Improved Lymphangiogenesis Inhibitormentioning

confidence: 99%

Mutation of Threonine 34 in Mouse Podoplanin-Fc Reduces CLEC-2 Binding and Toxicity in Vivo While Retaining Anti-lymphangiogenic Activity

Bianchi

Fischer

Yuen

et al. 2014

Journal of Biological Chemistry

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“…Podoplanin, a 38 kDa type I transmembrane glycoprotein, was identified as a platelet aggregation-inducing factor in cancer cells (3), and has been shown to be a useful immunohistochemical marker of lymphatic vessels. Lymphatic vessel density examined using an antibody to podoplanin has been reported to be a prognostic factor in lung cancer (4)(5)(6).…”

mentioning

confidence: 99%

Podoplanin Expression in Cancer-associated Fibroblasts Predicts Poor Prognosis in Patients with Squamous Cell Carcinoma of the Lung

Yurugi

Wakahara

Matsuoka

et al. 2017

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“…(1)(2)(3)(4)(5) PDPN is expressed in normal cells including renal podocytes, pulmonary type I alveolar cells, and lymphatic endothelial cells.…”

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confidence: 99%

“…(1)(2)(3)(4)(5) PDPN is expressed in normal cells including renal podocytes, pulmonary type I alveolar cells, and lymphatic endothelial cells. (4) PDPN activates platelet aggregation by binding to Ctype lectin-like receptor-2 (CLEC-2) on platelets, (6,7) and the PDPN-CLEC-2 interaction facilitates blood/lymphatic vessel separation.…”

mentioning

confidence: 99%

Podoplanin Expression in Canine Melanoma

Ogasawara

Honma

Kaneko

et al. 2016

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

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A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistry. Of interest, PMab-38 stained the lymphatic endothelial cells and cancer-associated fibroblasts in melanoma tissues, although it did not stain any lymphatic endothelial cells in normal tissues. PMab-38 could be useful for uncovering the function of PDPN in canine melanomas.Keywords: canine podoplanin, melanoma, monoclonal antibody, immunohistochemistry A type I transmembrane sialoglycoprotein, podoplanin (PDPN), is also known as gp40/T1a/Aggrus. (1)(2)(3)(4)(5) PDPN is expressed in normal cells including renal podocytes, pulmonary type I alveolar cells, and lymphatic endothelial cells.(4) PDPN activates platelet aggregation by binding to Ctype lectin-like receptor-2 (CLEC-2) on platelets, (6,7) and the PDPN-CLEC-2 interaction facilitates blood/lymphatic vessel separation.(8) The expression of human PDPN was reported in many tumors, including oral cancers,malignant brain tumors, (10)(11)(12) lung cancers, (13) esophageal cancers,malignant mesotheliomas, (15) testicular tumors, (16) and osteosarcomas.(17) PDPN expression is also associated with cancer metastasis and malignant progression. (6,10) We previously developed an anticanine PDPN monoclonal antibody (mAb), (18) which is useful for immunohistochemistry (IHC), flow cytometry, and Western blotting. Recently, we demonstrated that PMab-38 can recognize PDPN of canine squamous cell carcinomas using IHC.(19) Tumor cells in 15 out of 18 canine squamous cell carcinomas (83%) were stained by PMab-38 in IHC. Cancer-associated fibroblasts in 14 out of 18 cases (78%) were detected by PMab-38. In this study, we investigated whether canine melanoma was stained by PMab-38 because mouse PDPN expression and human PDPN expression were observed in melanomas.(20,21) Watanabe et al. reported that high expression of mouse PDPN is associated with the metastatic ability in metastatic variants of B16 melanomas. (20) We stained 10 canine oral melanomas, which are the most frequent oral cancers in dog. (22) As depicted in Figures 1 and 2A, melanoma cells were stained by PMab-38 in 9 of 10 cases. Although melanoma cells were not stained by PMab-38 in case 9 (Fig. 1), cancer-associated fibroblasts were recognized by PMab-38 (Fig. 2B). Both melanoma cells and cancer-associated fibroblasts were stained in case 5 (Fig. 1). Kan et al. reported that PDPN expression in cancer-associated fibroblasts correlates with aggressive behavior in human melanoma, (21) indicating that PDPN in cancer-associated fibroblasts of melanoma tissues might serve as a useful prognostic factor not only in human melanoma but ...

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Conservation of a platelet activating domain of Aggrus/podoplanin as a platelet aggregation-inducing factor

Cited by 122 publications

References 25 publications

Mutation of Threonine 34 in Mouse Podoplanin-Fc Reduces CLEC-2 Binding and Toxicity in Vivo While Retaining Anti-lymphangiogenic Activity

Mutation of Threonine 34 in Mouse Podoplanin-Fc Reduces CLEC-2 Binding and Toxicity in Vivo While Retaining Anti-lymphangiogenic Activity

Podoplanin Expression in Cancer-associated Fibroblasts Predicts Poor Prognosis in Patients with Squamous Cell Carcinoma of the Lung

Podoplanin Expression in Canine Melanoma

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