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High expression of S100A4 and endoglin is associated with metastatic disease in head and neck squamous cell carcinoma

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Abstract

The presence of cervical metastasis is responsible for high morbidity and mortality rates in individuals with head and neck squamous cell carcinoma (HNSCC). S100A4, a pleiotropic EF-hand calcium-binding protein, is expressed in various normal and cancer cell types. During cancer progression, molecular disturbances in S100A4 can modulate the activity and expression of pre-metastatic and metastatic genes. In this study, we investigated the association between S100A4 methylation status and protein expression as well as the expression of the S100A4 related-proteins annexin A2 (ANXA2), matrix metallopeptidase-9, and endoglin, for metastasis and other clinicopathological parameters in HNSCC. Formalin-fixed, paraffin-embedded blocks of metastatic and non-metastatic HNSCC and matched cervical lymph node (LN) samples (metastatic LN = mLN, non-metastatic = nmLN, and control LN (lymphadenitis) = cLN) were submitted for methylation specific-polymerase chain reaction and immunohistochemistry. Our results showed that S100A4 methylation status failed to demonstrate association with cervical metastasis and other clinicopathological factors related to HNSCC. HNSCC samples from patients that presented with metastatic disease showed high S100A4 and endoglin expression (p < 0.05). In conclusion, molecular disturbances in S100A4 and endoglin expression might regulate the formation of cervical metastasis in HNSCC.

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Acknowledgments

The authors are grateful for financial support from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Pesquisa (CNPq; process 478861/2012-5) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG; process APQ00650-12). AMB De-Paula, ALS Guimarães, SHS Santos, and RS Gomez are researchers fellows of the CNPq.

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The authors declare no Conflict of interests.

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Authors and Affiliations

  1. Nucleus of Epidemiological and Molecular Research Catrumano. Health Research Laboratory. Health Science Post-graduate Programme, Universidade Estadual de Montes Claros, Montes Claros, MG, 39401-001, Brazil

    Marcos Vinícius Macedo de Oliveira, Carlos Alberto de Carvalho Fraga, Lucas Oliveira Barros, Camila Santos Pereira, Sérgio Henrique Sousa Santos, Ricardo Santiago Gomez, André Luiz Sena Guimarães & Alfredo Maurício Batista De-Paula

  2. Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil

    Sérgio Henrique Sousa Santos

  3. Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD, 21201, USA

    John R. Basile

  4. Faculty of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil

    Ricardo Santiago Gomez

  5. Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, MG, 39401-001, Brazil

    André Luiz Sena Guimarães & Alfredo Maurício Batista De-Paula

  6. Programa de Pós-graduação em Ciências da Saúde. Sala 7. Hospital Universitário Clemente de Faria, Universidade Estadual de Montes Claros, Avenida Cula Mangabeira, 562. Bairro Santo Expedito, Montes Claros, MG, 39401-001, Brazil

    Alfredo Maurício Batista De-Paula

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  1. Marcos Vinícius Macedo de Oliveira
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  2. Carlos Alberto de Carvalho Fraga
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  3. Lucas Oliveira Barros
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  5. Sérgio Henrique Sousa Santos
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  8. André Luiz Sena Guimarães
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  9. Alfredo Maurício Batista De-Paula
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Correspondence to Alfredo Maurício Batista De-Paula.

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de Oliveira, M.V.M., de Carvalho Fraga, C.A., Barros, L.O. et al. High expression of S100A4 and endoglin is associated with metastatic disease in head and neck squamous cell carcinoma. Clin Exp Metastasis 31, 639–649 (2014). https://doi.org/10.1007/s10585-014-9655-4

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