HIF-1α is Overexpressed in Odontogenic Keratocyst Suggesting Activation of HIF-1α and NOTCH1 Signaling Pathways
Natacha Malu Miranda da Costa,
Caio Tadashi Saab Abe,
Geovanni Pereira Mitre,
Ricardo Alves Mesquita,
Maria Sueli da Silva Kataoka,
André Luis Ribeiro Ribeiro,
Ruy Gastaldoni Jaeger,
Sérgio de Melo Alves-Júnior,
Andrew Mark Smith,
João de Jesus Viana Pinheiro
Affiliations
Natacha Malu Miranda da Costa
Department of Buco-Maxillofacial Surgery and Traumatology and Periodontology, School of Dentistry of Ribeirão Preto, University of São Paulo, Av. do Café-Subsetor Oeste-11 (N-11), 14040-904 Ribeirão Preto, SP, Brazil
Caio Tadashi Saab Abe
Cell Culture Laboratory, School of Dentistry, Federal University of Pará (UFPA), Cidade Universitária Prof. José da Silveira Neto-R. Augusto Corrêa, 1-Guamá, 66075-110 Belém, PA, Brazil
Geovanni Pereira Mitre
Cell Culture Laboratory, School of Dentistry, Federal University of Pará (UFPA), Cidade Universitária Prof. José da Silveira Neto-R. Augusto Corrêa, 1-Guamá, 66075-110 Belém, PA, Brazil
Ricardo Alves Mesquita
Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, R. Prof. Moacir Gomes de Freitas, 688-Pampulha, 31270-901 Belo Horizonte, MG, Brazil
Maria Sueli da Silva Kataoka
Cell Culture Laboratory, School of Dentistry, Federal University of Pará (UFPA), Cidade Universitária Prof. José da Silveira Neto-R. Augusto Corrêa, 1-Guamá, 66075-110 Belém, PA, Brazil
André Luis Ribeiro Ribeiro
Cell Culture Laboratory, School of Dentistry, Federal University of Pará (UFPA), Cidade Universitária Prof. José da Silveira Neto-R. Augusto Corrêa, 1-Guamá, 66075-110 Belém, PA, Brazil
Ruy Gastaldoni Jaeger
Department of Cell and Developmental Biology Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1374-Butantã, 05508-900 São Paulo, SP, Brazil
Sérgio de Melo Alves-Júnior
Cell Culture Laboratory, School of Dentistry, Federal University of Pará (UFPA), Cidade Universitária Prof. José da Silveira Neto-R. Augusto Corrêa, 1-Guamá, 66075-110 Belém, PA, Brazil
Andrew Mark Smith
Department of Microbial Diseases, Eastman Dental Institute, University College London, 256 Grays Inn Rd, London WC1X 8LD, UK
João de Jesus Viana Pinheiro
Cell Culture Laboratory, School of Dentistry, Federal University of Pará (UFPA), Cidade Universitária Prof. José da Silveira Neto-R. Augusto Corrêa, 1-Guamá, 66075-110 Belém, PA, Brazil
Background: The odontogenic keratocyst (OKC) is an odontogenic cyst that shows aggressive and intriguing biological behavior. It is suggested that a hypoxic environment occurs in OKC, which led us to investigate the immunoexpression and location of hypoxia-inducible factor 1-alpha (HIF-1α) and other hypoxia-related proteins. Methods: Twenty cases of OKC were evaluated for the expression of Notch homolog 1 (NOTCH1), HIF-1α, disintegrin and metalloproteinase domain-containing protein 12 (ADAM-12), and heparin-binding epidermal growth factor-like growth factor (HBEGF) by immunohistochemistry and compared to eight control cases of calcifying odontogenic cystic (COC), orthokeratinized odontogenic cyst (OOC), and normal oral mucosa (OM) in basal and parabasal layers. Results: In OKC, all the proteins tested were expressed significantly higher in both basal (except for NOTCH1 and HBEGF in OOC) and suprabasal epithelial layers compared to controls. Looking at the epithelial layers within OKC, we observed an increased NOTCH1 and HIF-1α expression in parabasal layers. Conclusions: These results suggest that hypoxia occurs more intensively in OKC compared to COC, OM, and OOC. Hypoxia appeared to be stronger in parabasal layers as observed by higher HIF-1α expression in upper cells. Overexpression of NOTCH1, ADAM-12, and HBEGF in OKC was observed, which suggests that microenvironmental hypoxia could potentially regulate the expression of hypoxia-related proteins, and consequently, its clinical and biological behavior.
