Characterization of Anti-podoplanin Monoclonal Antibodies: Critical Epitopes for Neutralizing the Interaction Between Podoplanin and CLEC-2

Ogasawara, Satoshi; Kaneko, Mika K.; Price, Janet E.; Kato, Yoshinori

doi:10.1089/hyb.2008.0017

Cited by 74 publications

(71 citation statements)

References 24 publications

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“…36 In addition, we confirmed that the PDPN-mediated adhesion was calcium dependent without any expressional switching All data are means±s.e. from triplicate experiments.…”

Section: Discussionsupporting

confidence: 68%

Podoplanin-mediated cell adhesion through extracellular matrix in oral squamous cell carcinoma

Tsuneki

Yamazaki

Maruyama

et al. 2013

Laboratory Investigation

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Podoplanin (PDPN), one of the representative mucin-like type-I transmembrane glycoproteins specific to lymphatic endothelial cells, is expressed in various cancers including squamous cell carcinoma (SCC). On the basis of our previous studies, we have developed the hypothesis that PDPN functions in association with the extracellular matrix (ECM) from the cell surface side. The aim of this study was to elucidate the molecular role of PDPN in terms of cell adhesion, proliferation, and migration in oral SCC cells. Forty-four surgical specimens of oral SCC were used for immunohistochemistry for PDPN, and the expression profiles were correlated with their clinicopathological properties. Using ZK-1, a human oral SCC cell system, and five other cell systems, we examined PDPN expression levels by immunofluorescence, western blotting, and real-time PCR. The effects of transient PDPN knockdown by siRNA in ZK-1 were determined for cellular functions in terms of cell proliferation, adhesion, migration, and invasion in association with CD44 and hyaluronan. Cases without PDPN-positive cells were histopathologically classified as less-differentiated SCC, and SCC cells without PDPN more frequently invaded lymphatics. Adhesive properties of ZK-1 were significantly inhibited by siRNA, and PDPN was shown to collaborate with CD44 in cell adhesion to tether SCC cells with hyaluronan-rich ECM of the narrow intercellular space as well as with the stromal ECM. There was no siRNA effect in migration. We have demonstrated the primary function of PDPN in cell adhesion to ECM, which is to secondarily promote oral SCC cell proliferation.Laboratory Investigation (2013) 93, 921-932;

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“…36 In addition, we confirmed that the PDPN-mediated adhesion was calcium dependent without any expressional switching All data are means±s.e. from triplicate experiments.…”

Section: Discussionsupporting

confidence: 68%

Podoplanin-mediated cell adhesion through extracellular matrix in oral squamous cell carcinoma

Tsuneki

Yamazaki

Maruyama

et al. 2013

Laboratory Investigation

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“…14 The membranes were incubated with an anti-human podoplanin antibody (NZ-1; AngioBio, Del Mar, CA) 30 or an anti-␤-actin antibody (Sigma, St. Louis, MO), followed by a horseradish peroxidase-conjugated secondary antibody, and developed using the ECL system (GE Healthcare, Chalfont St. Giles, Buckinghamshire, England, UK).…”

Section: Western Blot Analysismentioning

confidence: 99%

Podoplanin Is Regulated by AP-1 and Promotes Platelet Aggregation and Cell Migration in Osteosarcoma

Kunita

Kashima

Ohazama

et al. 2011

The American Journal of Pathology

101

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Podoplanin is a type-I transmembrane sialomucinlike protein, which is expressed in a wide range of cell types and is involved in platelet aggregation and tumor metastasis. Here, we investigated the function, regulation, and expression of podoplanin in osteosarcoma. Podoplanin expression was observed in three osteosarcoma cell lines (MG-63, HOS, and U-2 OS) with platelet aggregation-inducing ability, which was blocked by podoplanin small-interfering RNA or a neutralizing antibody. Overexpression of podoplanin in nonmetastatic Dunn osteosarcoma cells promoted cell migration without attenuating cell proliferation. Both podoplanin and TGF-␤1 were up-regulated by c-Fos induction in MC3T3-E1 osteoblastic cells, and were highly expressed in c-Fos transgenic mouse osteosarcomas and c-Fos-transformed osteosarcoma cell lines. Immunohistochemistry of human osteosarcoma tissue microarrays (n ‫؍‬ 133) showed staining of tumor cells embedded in an excess of irregular neoplastic bone matrix in 100% of tumors undergoing so-called "normalization/maturation." Podoplanin was also expressed in osteosarcoma subtypes, with 65% of osteoblastic, 100% of chondroblastic, and 79% of fibroblastic tumors. CD44 and pERM immunohistochemistry showed coexpression with podoplanin in both mouse and human osteosarcoma. Podoplanin expression was significantly higher in metastatic osteosarcomas (n ‫؍‬ 6) than in primary osteosarcomas (n ‫؍‬ 10). Our data suggest that podoplanin, which is not expressed in normal osteoblasts but in osteocytes, is aberrantly expressed in transformed osteoblasts and in osteosarcoma, and is under AP-1 transcriptional control. Thus podoplanin is a candidate molecule for ther- Osteosarcoma (OS) is the most common primary malignant bone tumor, with a high tendency to metastasize to the lung. Despite recent advances in modern chemotherapy, the average survival after a recurrence in distant organs is less than 1 year.1 In contrast, of patients who present with no metastasis, approximately 70% will be long-term survivors.2 Therefore, there is a strong necessity to better understand the molecular mechanisms of metastasis to deliver innovative life-saving and life-enhancing therapies to patients.Platelet aggregation is one of the crucial steps involved during the sequential tumor metastasis process to escape from the host immune system and form tumor emboli in distant organs. Several earlier studies have shown that platelet aggregating capability of tumor cells from colon cancer and melanoma is correlated with their metastatic potential in vivo.3-5 Podoplanin, a type-I transmembrane sialomucin-like glycoprotein, is a platelet aggregation-inducing factor 6 that is expressed in a wide range of tumors 7-9 and has been reported to be associated with poor outcome of oral and esophageal squamous cell carcinomas.10,11 Podoplanin promotes cell migration and cell invasion, 9,12 and also plays a key role in epithelial-mesenchymal transition in Madin-Darby canine kidney (MDCK) type-II cells.

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“…The podoplanin is a main factor for platelet aggregation induced by the glioblastoma cell line LN319 and a NZ-1 antibody for the PLAG domain completely inhibits podoplanin-induced platelet aggregation because of the neutralization between podoplanin and CLEC-2 [58,61]. In an experimental mouse model podoplanin promoted hematogenous metastasis to the lung and the antipodoplanin antibody NZ-1 suppressed both the podoplanin-CELC-2 interaction and podoplanin-induced pulmonary metastasis [59,61,64,65]. Possibility of the clinical application on the neutralization of podoplanin-CLEC-2 interaction inducing hematogenous metastasis should be settled early.…”

Section: Molecular Biological Function Of Podoplaninmentioning

confidence: 99%

New trends in the study of podoplanin as a cell morphological regulator

Sawa

2010

Japanese Dental Science Review

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Characterization of Anti-podoplanin Monoclonal Antibodies: Critical Epitopes for Neutralizing the Interaction Between Podoplanin and CLEC-2

Cited by 74 publications

References 24 publications

Podoplanin-mediated cell adhesion through extracellular matrix in oral squamous cell carcinoma

Podoplanin-mediated cell adhesion through extracellular matrix in oral squamous cell carcinoma

Podoplanin Is Regulated by AP-1 and Promotes Platelet Aggregation and Cell Migration in Osteosarcoma

New trends in the study of podoplanin as a cell morphological regulator

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