Podoplanin emerges as a functionally relevant oral cancer biomarker and therapeutic target

Retzbach, Edward P.; Sheehan, Stephanie A.; Nevel, Evan; Batra, Amber; Tran, Peter; Nguyen, Angels; Kato, Yukinari; Baredes, Soly; Fatahzadeh, Mahnaz; Shienbaum, Alan J.; Goldberg, Gary S.

doi:10.1016/j.oraloncology.2018.01.011

Cited by 43 publications

(39 citation statements)

References 164 publications

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“…As shown in Figure 1c and Figure S1, DDR1 staining is more evident in samples with ALI than those without, whereas PDPN expression is uniquely localized in the invasion front or outward regions of ALI positive tumor sections. Note that the PDPN staining is reminiscent of poor prognosis markers previously documented in oral cancer and premalignant lesions [24,26,35]. .…”

Section: Clinical Relevance Of Ddr1 Overexpression and Alimentioning

confidence: 87%

“…Mechanistically, collective cell migration requires an array of basal epithelium molecules, adherent junctions and cadherins to maintain integrity and cell-cell coordination during collective movement [20][21][22]. At molecular level, DDR1, PARD3, PARD6, CDH1, and CLDN11 are responsible for maintaining cell-cell junctions during cluster advancement [17,23]; PDPN, a mucin-like transmembrane protein frequently expressed in the leading edge of tumor, is implicated in guiding movement direction [24][25][26]; matrix metalloproteinases (MMPs) and basement membrane type IV collagens are required for track clearing and secondary ECM remodeling, respectively [27]. Based on histological evidence, collective cancer cell migration is likely to be a critical step in cancer metastasis [28].…”

Section: Of 18mentioning

confidence: 99%

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Discoidin Domain Receptor-1 (DDR1) is Involved in Angiolymphatic Invasion in Oral Cancer

Chen

Tsai

et al. 2020

Cancers

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The discoidin domain receptor-1 (DDR1) is a non-integrin collagen receptor recently implicated in the collective cell migration of other cancer types. Previously, we identified an elevated expression of DDR1 in oral squamous cell carcinoma (OSCC) cells. Through the data mining of a microarray dataset composed of matched tumor-normal tissues from forty OSCC patients, we distilled overexpressed genes statistically associated with angiolymphatic invasion, including DDR1, COL4A5, COL4A6 and PDPN. Dual immunohistochemical staining further confirmed the spatial locations of DDR1 and PDPN in OSCC tissues indicative of collective cancer cell invasion. An elevated DDR1 expression at both the transcription and protein level was observed by treating keratinocytes with collagen of fibrillar or basement membrane types. In addition, inhibition of DDR1 kinase activity in OSCC TW2.6 cells disrupted cell cohesiveness in a 2D culture, reduced spheroid invasion in a collagen gel matrix, and suppressed angiolymphatic invasion in xenograft tissues. Taken together, these results suggest that collagen deposition in the affected tissues followed by DDR1 overexpression could be central to OSCC tumor growth and angiolymphatic invasion. Thus, DDR1 inhibitors are potential therapeutic compounds in restraining oral cancer, which has not been previously explored.

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Section: Clinical Relevance Of Ddr1 Overexpression and Alimentioning

confidence: 87%

Section: Of 18mentioning

confidence: 99%

Discoidin Domain Receptor-1 (DDR1) is Involved in Angiolymphatic Invasion in Oral Cancer

Chen

Tsai

et al. 2020

Cancers

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“…(12) In contrast, PMab-38 showed cancer specificity in immunohistochemistry using canine tissues (2) in the same pattern with anti-human PDPN (hPDPN) cancer-specific mAbs, such as LpMab-2 (7,13) and LpMab-23. (6,14,15) We previously showed that Thr55-Leu64 peptide of hPDPN, especially O-glycan attached in Thr55 and Ser56 of hPDPN, is a critical epitope of LpMab-2. (7) We further showed that Gly54-Leu64 peptide of hPDPN is a critical epitope of LpMab-23.…”

Section: Figmentioning

confidence: 99%

“…(1) However, higher expression of PDPN has been observed in different tumor types, including squamous cell carcinoma, (2) melanoma, (3) glioblastoma, (4) and mesothelioma. (5) Recent clinical studies have provided evidence of associations between increased PDPN expression, poor prognosis, and cancer metastasis, (6) indicating that the establishment and production of anti-PDPN monoclonal antibodies (mAbs) are necessary for developing novel therapeutic strategies against cancer development and progression to metastasis. (7) Dog podoplanin (dPDPN) was first reported as gp40.…”

Section: Introductionmentioning

confidence: 99%

Epitope Mapping of Monoclonal Antibody PMab-48 Against Dog Podoplanin

Yamada

Kaneko

Itai

et al. 2018

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

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Podoplanin (PDPN), a type I transmembrane sialoglycoprotein, is expressed on normal renal podocytes, pulmonary type I alveolar cells, and lymphatic endothelial cells. Increased expression of PDPN in cancers is associated with poor prognosis and hematogenous metastasis through interactions with C-type lectin-like receptor 2 (CLEC-2) on platelets. We previously reported a novel PMab-48 antibody, which is an anti-dog PDPN (dPDPN) monoclonal antibody (mAb) recognizing PDPN expressed in lymphatic endothelial cells. However, the binding epitope of PMab-48 is yet to be clarified. In this study, an enzyme-linked immunosorbent assay and flow cytometry were used to investigate epitopes of PMab-48. The results revealed that the critical epitope of PMab-48 comprises Asp29, Asp30, Ile31, Ile32, and Pro33 of dPDPN.

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“…8 It has been associated emphatically with tumor invasion and metastasis. 9 Interestingly, Atsumi, et al 10 (2008) have shown that podoplanin-positive cancer cells exhibited stem cell-like properties, as they had the ability to undergo repopulation and give rise to heterogenous cancer cell population. 10 Few studies have analyzed the expression of SOX2 and podoplanin in the progression of oral squamous cell carcinomas.…”

Section: Introductionmentioning

confidence: 99%

Association of the co-expression of SOX2 and Podoplanin in the progression of oral squamous cell carcinomas - an immunohistochemical study

2019

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Association of the co-expression of SOX2 and Podoplanin in the progression of oral squamous cell carcinomas -an immunohistochemical study SOX2 is a transcription factor related to the maintenance of stem cells in a pluripotent state. Podoplanin is a type of transmembrane sialoglycoprotein, which plays an important role in tumor progression and metastasis. This study aims to determine association of SOX2 and podoplanin expression in the progression of oral squamous cell carcinomas and to elucidate the association between two proteins. Methodology: The immunohistochemical expression of SOX2 and podoplanin were evaluated in 60 cases of primary oral squamous cell carcinomas. The correlation between the SOX2 and podoplanin expression and the clinicopathological features of the tumors and the patient outcomes were assessed. Results: The expression of SOX2 was seen in 38/60 (63%) of the cases and the expression for podoplanin was seen in 45/60 (75%) cases. There was a significant inverse correlation between the expression of SOX2 and podoplanin with the tumor grade (p=0.002 and p=0.017, respectively). There was a high expression of SOX2 in 9/13 cases that presented with disease free survival. Survival analysis showed that a high expression of SOX2 correlated positively (p=0.043) with the disease-free survival. There was a significant positive association between the pattern of SOX2 and podoplanin expression (p=0.002). Conclusion: A high expression of SOX2 was associated with better disease-free survival. The expression of podoplanin was associated with the degree of differentiation of the tumors.Analysis of these biomarkers can aid in the prognosis and treatment of oral squamous cell carcinomas.

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Podoplanin emerges as a functionally relevant oral cancer biomarker and therapeutic target

Cited by 43 publications

References 164 publications

Discoidin Domain Receptor-1 (DDR1) is Involved in Angiolymphatic Invasion in Oral Cancer

Discoidin Domain Receptor-1 (DDR1) is Involved in Angiolymphatic Invasion in Oral Cancer

Epitope Mapping of Monoclonal Antibody PMab-48 Against Dog Podoplanin

Association of the co-expression of SOX2 and Podoplanin in the progression of oral squamous cell carcinomas - an immunohistochemical study

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