Inflammation and Cancer: Role of Annexin A1 and FPR2/ALX in Proliferation and Metastasis in Human Laryngeal Squamous Cell Carcinoma

Inflammation and Cancer: Role of Annexin A1 and FPR2/ALX in Proliferation and Metastasis in Human Laryngeal Squamous Cell Carcinoma

Autor Gastardelo, Thais Santana Autor UNIFESP Google Scholar
Cunha, Bianca Rodrigues Google Scholar
Raposo, Luis Sergio Google Scholar
Maniglia, Jose Victor Google Scholar
Cury, Patricia Maluf Google Scholar
Rodrigues Lisoni, Flavia Cristina Google Scholar
Tajara, Eloiza Helena Google Scholar
Oliani, Sonia Maria Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
São Paulo State Univ UNESP
Resumo The anti-inflammatory protein annexin A1 (ANXA1) has been associated with cancer progression and metastasis, suggesting its role in regulating tumor cell proliferation. We investigated the mechanism of ANXA1 interaction with formylated peptide receptor 2 (FPR2/ALX) in control, peritumoral and tumor larynx tissue samples from 20 patients, to quantitate the neutrophils and mast cells, and to evaluate the protein expression and co-localization of ANXA1/FPR2 in these inflammatory cells and laryngeal squamous cells by immunocytochemistry. in addition, we performed in vitro experiments to further investigate the functional role of ANXA1/FPR2 in the proliferation and metastasis of Hep-2 cells, a cell line from larynx epidermoid carcinoma, after treatment with ANXA1(2-26) (annexin A1 N-terminal-derived peptide), Boc2 (antagonist of FPR) and/or dexamethasone. Under these treatments, the level of Hep-2 cell proliferation, pro-inflammatory cytokines, ANXA1/FPR2 co-localization, and the prostaglandin signalling were analyzed using ELISA, immunocytochemistry and real-time PCR. An influx of neutrophils and degranulated mast cells was detected in tumor samples. in these inflammatory cells of peritumoral and tumor samples, ANXA1/FPR2 expression was markedly exacerbated, however, in laryngeal carcinoma cells, this expression was downregulated. ANXA1(2-26) treatment reduced the proliferation of the Hep-2 cells, an effect that was blocked by Boc2, and up-regulated ANXA1/FPR2 expression. ANXA1(2-26) treatment also reduced the levels of pro-inflammatory cytokines and affected the expression of metalloproteinases and EP receptors, which are involved in the prostaglandin signalling. Overall, this study identified potential roles for the molecular mechanism of the ANXA1/FPR2 interaction in laryngeal cancer, including its relationship with the prostaglandin pathway, providing promising starting points for future research. ANXA1 may contribute to the regulation of tumor growth and metastasis through paracrine mechanisms that are mediated by FPR2/ALX. These data may lead to new biological targets for therapeutic intervention in human laryngeal cancer.
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Número do financiamento FAPESP: 2008/08187-4
FAPESP: 2008/01655-2
CNPq: 302768/2010-6
Data 2014-12-09
Publicado em Plos One. San Francisco: Public Library Science, v. 9, n. 12, 23 p., 2014.
ISSN 1932-6203 (Sherpa/Romeo, fator de impacto)
Editor Public Library Science
Extensão 23
Fonte http://dx.doi.org/10.1371/journal.pone.0111317
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000347515300001
URI http://repositorio.unifesp.br/handle/11600/38549

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