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Int J Mol Sci. 2019 Apr 23;20(8). pii: E1973. doi: 10.3390/ijms20081973.

Notch Signaling Affects Oral Neoplasm Cell Differentiation and Acquisition of Tumor-Specific Characteristics.

Author information

1
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan. keisuke1@okayama-u.ac.jp.
2
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan. gmd422094@s.okayama-u.ac.jp.
3
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan. de18018@s.okayama-u.ac.jp.
4
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan. de20052@s.okayama-u.ac.jp.
5
Department of Oral Pathology, School of Dentistry, Aichi Gakuin University, Nagoya 464-8650, Japan. hatsu@dpc.aichi-gakuin.ac.jp.
6
Hard Tissue Pathology Unit, Matsumoto Dental University Graduate School of Oral Medicine, Shiojiri 399-0781, Japan. toshiyuki.kawakami@mdu.ac.jp.
7
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan. jin@okayama-u.ac.jp.

Abstract

Histopathological findings of oral neoplasm cell differentiation and metaplasia suggest that tumor cells induce their own dedifferentiation and re-differentiation and may lead to the formation of tumor-specific histological features. Notch signaling is involved in the maintenance of tissue stem cell nature and regulation of differentiation and is responsible for the cytological regulation of cell fate, morphogenesis, and/or development. In our previous study, immunohistochemistry was used to examine Notch expression using cases of odontogenic tumors and pleomorphic adenoma as oral neoplasms. According to our results, Notch signaling was specifically associated with tumor cell differentiation and metaplastic cells of developmental tissues. Notch signaling was involved in the differentiation of the ductal epithelial cells of salivary gland tumors and ameloblast-like cells of odontogenic tumors. However, Notch signaling was also involved in squamous metaplasia, irrespective of the type of developmental tissue. In odontogenic tumors, Notch signaling was involved in epithelial-mesenchymal interactions and may be related to tumor development and tumorigenesis. This signaling may also be associated with the malignant transformation of ameloblastomas. Overall, Notch signaling appears to play a major role in the formation of the characteristic cellular composition and histological features of oral neoplasms, and this involvement has been reviewed here.

KEYWORDS:

cell differentiation; epithelial-mesenchymal interaction; immunohistochemistry; malignant transformation; notch signaling; odontogenic tumor; pleomorphic adenoma

PMID:
31018488
DOI:
10.3390/ijms20081973
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