Podoplanin: A Novel Marker for Oral Cancer Risk in Patients With Oral Premalignancy

Kawaguchi, Hidetoshi; El‐Naggar, Adel K.; Papadimitrakopoulou, Vali; Ren, Hening; Fan, You-Hong; Feng, Lei; Lee, John; Kim, Edward; Hong, Waun Ki; Lippman, Scott M.; Li, Mao

doi:10.1200/jco.2007.13.4072

Cited by 178 publications

(229 citation statements)

References 22 publications

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“…The result contradicted that of previous reports in which the PDPN expression itself was emphasized in malignancies, yet no detailed attention has paid to its relation to cell adhesion. [10][11][12]35 We would like to suggest the possibility that the loss of PDPN expression is because of the decreased differentiation of oral SCC cells, which also results in their invasive or scattering tendencies.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8][9]34 In oral cancer, PDPN expression has been related to poor clinical outcomes, including lymph node metastasis or to malignant transformation of precancerous lesions, although its molecular function has not been well understood. [10][11][12][13]35 To elucidate its function, we carried out comparative immunohistochemical studies between PDPN and the other molecules, which are related to cell proliferation or differentiation in oral mucosal malignancies 13 or odontogenic tumors. 7 Its expression profile in oral CIS was almost identical to that of SCC, and the immunohistochemistry for PDPN was helpful in the differential diagnosis of CIS from epithelial dysplasia.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8][9][10][11] In the field of oral cancer, PDPN has also been regarded as a biomarker in predicting the risk of cancer development and poor clinical outcome. [10][11][12] We have also shown the PDPN expression profiles to be a useful immunohistochemical aid in the differential diagnosis of oral carcinoma in situ (CIS) from epithelial dysplasia because PDPN positive ( þ ) cells are distributed more widely in CIS than in epithelial dysplasia, overlapping with Ki-67 þ -proliferating cell zones. 13 In order to provide a background to the cellproliferating potentials of oral CIS, we have demonstrated the characteristic intercellular deposition and turnover of perlecan, one of the extracellular matrix (ECM) molecules, which results in the widening of intercellular space of the epithelial compartment.…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Tsuneki

Yamazaki

Maruyama

et al. 2013

Laboratory Investigation

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“…152,157 PDPN is predominantly found at the invasive front of many tumors, which is consistent with its role in promoting malignant invasion. 152,158 For example, PDPN expression is strongly induced in about 40% of breast cancers, 158,159 over 50% of oral cancers, 160,161 and about 80% of skin cancers. 162,163 Antibodies against PDPN and a PDPN interacting partner (tetraspanin CD9) can inhibit lung metastasis of CHO cells transfected with PDPN.…”

Section: Src and Downstream Chemotherapeutic Targetsmentioning

confidence: 99%

Src Points the Way to Biomarkers and Chemotherapeutic Targets

Krishnan¹,

Miller

Goldberg³

2012

Genes & Cancer

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The role of Src in tumorigenesis has been extensively studied since the work of Peyton Rous over a hundred years ago. Src is a non-receptor tyrosine kinase that plays key roles in signaling pathways controlling tumor cell growth and migration. Src regulates the activities of numerous molecules to induce cell transformation. However, transformed cells do not always migrate and realize their tumorigenic potential. They can be normalized by surrounding nontransformed cells by a process called contact normalization. Tumor cells need to override contact normalization to become malignant or metastatic. In this review, we discuss the role of Src in cell migration and contact normalization, with emphasis on Cas and Abl pathways. This paradigm illuminates several chemotherapeutic targets and may lead to the identification of new biomarkers and the development of effective anticancer treatments.

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“…These include (but are not limited to) podoplainin [26], deltaNp63 [17], cyclin D1 genotypes [27], specific mRNA expression [28] and DNA methylation [29] profiles, miRNA-31 [30], human telomerase RNA component (hTERC) gene copy number [31], ABCG2 and BMI-1 expression [32], and EGFR protein, mRNA expression and gene copy number gains [33]. Most of these studies, however, consisted of retrospective analyses, including varying (but often limited) number of specimens, without validation on i ndependent datasets.…”

Section: Prognostic Markers Beyond Lohmentioning

confidence: 99%

Prognostic Factors, Predictive Markers and Cancer Biology: The Triad for Successful Oral Cancer Chemoprevention

Novaes

William

2016

Future Oncol.

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Oral squamous cell carcinomas represent a significant cancer burden worldwide. Unfortunately, chemoprevention strategies investigated to date have failed to produce an agent considered standard of care to prevent oral cancers. Nonetheless, recent advances in clinical trial design may streamline drug development in this setting. In this manuscript, we review some of these improvements, including risk prediction tools based on molecular markers that help select patients most suitable for chemoprevention. We also discuss the opportunities that novel preclinical models and modern molecular profiling techniques will bring to the prevention field in the near future, and propose a clinical trials framework that incorporates molecular prognostic factors, predictive markers and cancer biology as a roadmap to improve chemoprevention strategies for oral cancers. A major global health concern, oral squamous cell carcinoma (OSCC) is currently the 13th most common cancer worldwide, with an estimate of 300,000 new cases, and 145,000 deaths each year [1]. Tobacco, alcohol and/or betel nut exposure are well-established risk factors for OSCC. Interruption of carcinogen use is an obvious key intervention to reduce oral cancer incidence ('primary' prevention). Nonetheless, OSCC risk remains elevated even after alcohol and tobacco cessation and may take up to 20 years to reach baseline levels [2] illustrating the need for development of approaches that can interrupt/reverse the process of carcinogenesis after initiation, but before full malignant transformation. Furthermore, an increase in the incidence of oral cancer in women with no clear etiologic factors has been observed [3], supporting the need for improved understanding of molecular pathways dysregulation that lead to cancer and how they could be targeted for OSSC prevention.Oral potentially malignant lesions (OPMLs) are often clinically characterized as leukoplakia and/or erythroplakia. Histologically, these lesions frequently exhibit hyperplasia, hyperkeratosis and/or varying degrees of dysplasia (i.e., intraepithelial neoplasias [IEN]). OPMLs are not obligate precursors of oral cancers, but they are estimated to precede development of at least 7% of OSCC [4] OPMLs are in and of themselves risk factors for oral cancer, but have a variable frequency of malignant transformation, depending on other clinical, demographic, etiologic, histological and/or molecular features [5]. The anatomic accessibility of OPMLs for examination and biopsies provides an opportunity for clinical and translational studies of oral carcinogenesis. In this review, we will summarize the recent advances and future perspectives of molecularly focused strategies of oral cavity cancers chemoprevention, many of which stem from OPML-based research. We will specifically

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Podoplanin: A Novel Marker for Oral Cancer Risk in Patients With Oral Premalignancy

Abstract: Podoplanin is frequently expressed in OPL. Together with histology, podoplanin may serve as a powerful biomarker to predict the risk for oral cancer development in patients with OPL.

Cited by 178 publications

References 22 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

Src Points the Way to Biomarkers and Chemotherapeutic Targets

Prognostic Factors, Predictive Markers and Cancer Biology: The Triad for Successful Oral Cancer Chemoprevention

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