Please use this identifier to cite or link to this item: http://repositorio.unifesp.br/11600/38549
Title: Inflammation and Cancer: Role of Annexin A1 and FPR2/ALX in Proliferation and Metastasis in Human Laryngeal Squamous Cell Carcinoma
Authors: Gastardelo, Thais Santana [UNIFESP]
Cunha, Bianca Rodrigues
Raposo, Luis Sergio
Maniglia, Jose Victor
Cury, Patricia Maluf
Rodrigues Lisoni, Flavia Cristina
Tajara, Eloiza Helena
Oliani, Sonia Maria [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
São Paulo State Univ UNESP
Issue Date: 9-Dec-2014
Publisher: Public Library Science
Citation: Plos One. San Francisco: Public Library Science, v. 9, n. 12, 23 p., 2014.
Abstract: 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.
URI: http://repositorio.unifesp.br/handle/11600/38549
ISSN: 1932-6203
Other Identifiers: http://dx.doi.org/10.1371/journal.pone.0111317
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