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Podoplanin expression during dysplasia–carcinoma sequence in the oral cavity

  • Research Article
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Tumor Biology

Abstract

Human podoplanin, a type-1 transmembrane sialomucin-like glycoprotein, is involved in cell migration, tumor cell invasion, and metastasis. However, the role of the protein in squamous cell carcinoma (SCC) has been unclear and immunohistochemical reactivity for podoplanin differs from organ-to-organ. In the present study, immunohistochemical and molecular biological analyses were performed to examine the importance of podoplanin expression in oral precancerous and cancerous lesions and metastases. We immunohistochemically investigated the expression of podoplanin in 103 precancerous lesions, 69 primary oral squamous cell carcinomas (OSCCs), and 32 metastases, and that of E-cadherin and vimentin in primary OSCCs with metastasis. Furthermore, human OSCC-derived cell lines preincubated with fibrous growth factor-basic, epidermal growth factor (EGF), and tumor growth factor-β1 were subjected to real-time reverse transcription polymerase chain reaction. Immunoreactivity for podoplanin was detected in 89 (86.4%) of the precancerous lesions and the intensity was correlated with the degree of epithelial dysplasia (P = 0.016). Enhanced podoplanin expression was observed in 66 (95.7%) of the OSCCs and was significantly associated with a poor pathologic grade of differentiation (P = 0.020). Epithelial–mesenchymal transition was observed in 18 (58.1%) of the primary OSCCs with metastasis to regional lymph nodes. Messenger RNA for podoplanin was markedly increased after treatment with EGF in three OSCC cell lines. The present findings suggest that podoplanin is associated with tumor development via the oral dysplasia–carcinoma sequence and could be involved in a signaling pathway governing tumor growth and invasion in OSCC.

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Abbreviations

SCC:

Squamous cell carcinoma

OSCC:

Oral SCC

HNSCC:

Head and neck SCC

bFGF:

Fibrous growth factor-basic

EGF:

Epidermal growth factor

TGF-β1:

Tumor growth factor-β1

EMT:

Epithelial–mesenchymal transition

pN+ :

With pathological node metastasis

pN− :

Without pathological node metastasis

EGFR:

Epidermal growth factor receptor

Cas:

Crk-associated substrate

SIN 3:

Squamous intraepithelial neoplasia 3

H&E:

Hematoxylin and eosin

T stage:

Primary tumor stage

N stage:

Regional lymph nodes stage

UICC:

International Union against Cancer

CIS:

Carcinoma in situ

GAPDH:

Glyceraldehyde-dehydrogenase

PLCγ-1:

Phospholipase Cγ-1

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Authors and Affiliations

  1. Division of Pathology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Keyakidai, Sakado, Saitama, 350-0283, Japan

    Harumi Inoue, Yuji Miyazaki, Kentaro Kikuchi, Noriaki Yoshida, Fumio Ide & Kaoru Kusama

  2. Division of Microbiology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, Sakado, Saitama, Japan

    Yoshihiro Ohmori

  3. Division of Biochemistry, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, Sakado, Saitama, Japan

    Akihito Tomomura

  4. Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Saitama, Japan

    Hideaki Sakashita

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  1. Harumi Inoue
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Correspondence to Harumi Inoue.

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Inoue, H., Miyazaki, Y., Kikuchi, K. et al. Podoplanin expression during dysplasia–carcinoma sequence in the oral cavity. Tumor Biol. 33, 183–194 (2012). https://doi.org/10.1007/s13277-011-0261-7

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  • DOI: https://doi.org/10.1007/s13277-011-0261-7

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