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Protumor Steering of Cancer Inflammation by p50 NF-κB Enhances Colorectal Cancer Progression.
Porta, Chiara; Ippolito, Alessandro; Consonni, Francesca Maria; Carraro, Lorenzo; Celesti, Giuseppe; Correale, Carmen; Grizzi, Fabio; Pasqualini, Fabio; Tartari, Silvia; Rinaldi, Maurizio; Bianchi, Paolo; Balzac, Fiorella; Vetrano, Stefania; Turco, Emilia; Hirsch, Emilio; Laghi, Luigi; Sica, Antonio.
Afiliação
  • Porta C; Department of Pharmaceutical Sciences, Università degli Studi del Piemonte Orientale "Amedeo Avogadro," Novara, Italy. antonio.sica@uniupo.it chiara.porta@uniupo.it.
  • Ippolito A; Department of Pharmaceutical Sciences, Università degli Studi del Piemonte Orientale "Amedeo Avogadro," Novara, Italy.
  • Consonni FM; Department of Pharmaceutical Sciences, Università degli Studi del Piemonte Orientale "Amedeo Avogadro," Novara, Italy.
  • Carraro L; Department of Pharmaceutical Sciences, Università degli Studi del Piemonte Orientale "Amedeo Avogadro," Novara, Italy.
  • Celesti G; Humanitas Clinical and Research Center, Rozzano, Italy.
  • Correale C; Humanitas Clinical and Research Center, Rozzano, Italy.
  • Grizzi F; Humanitas Clinical and Research Center, Rozzano, Italy.
  • Pasqualini F; Humanitas Clinical and Research Center, Rozzano, Italy.
  • Tartari S; Humanitas Clinical and Research Center, Rozzano, Italy.
  • Rinaldi M; Department of Pharmaceutical Sciences, Università degli Studi del Piemonte Orientale "Amedeo Avogadro," Novara, Italy.
  • Bianchi P; Humanitas Clinical and Research Center, Rozzano, Italy.
  • Balzac F; Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, Torino, Italy.
  • Vetrano S; Humanitas Clinical and Research Center, Rozzano, Italy.
  • Turco E; Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, Torino, Italy.
  • Hirsch E; Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, Torino, Italy.
  • Laghi L; Humanitas Clinical and Research Center, Rozzano, Italy.
  • Sica A; Department of Pharmaceutical Sciences, Università degli Studi del Piemonte Orientale "Amedeo Avogadro," Novara, Italy. antonio.sica@uniupo.it chiara.porta@uniupo.it.
Cancer Immunol Res ; 6(5): 578-593, 2018 05.
Article em En | MEDLINE | ID: mdl-29588321
ABSTRACT
Although tumor-associated macrophages (TAM) display a M2-skewed tumor-promoting phenotype in most cancers, in colorectal cancer, both TAM polarization and its impact remain controversial. We investigated the role of the M2-polarizing p50 NF-κB subunit in orchestrating TAM phenotype, tumor microenvironment composition, and colorectal cancer progression. We first demonstrated, by parallel studies in colitis-associated cancer (CAC) and in genetically driven ApcMin mouse models, that the p50-dependent inhibition of M1-polarized gut inflammation supported colorectal cancer development. In accordance with these studies, p50-/- mice displayed exacerbated CAC with fewer and smaller tumors, along with enhanced levels of M1/Th1 cytokines/chemokines, including IL12 and CXCL10, whose administration restrained CAC development in vivo The inflammatory profile supporting tumor resistance in colons from p50-/- tumor bearers correlated inversely with TAM load and positively with both recruitment of NK, NKT, CD8+ T cells and number of apoptotic tumor cells. In agreement, myeloid-specific ablation of p50 promoted tumor resistance in mice, whereas in colorectal cancer patients, a high number of p50+ TAMs at the invasive margin was associated with decreased IL12A and TBX21 expression and worse postsurgical outcome. Our findings point to p50 involvement in colorectal cancer development, through its engagement in the protumor activation of macrophages, and identify a candidate for prognostic and target therapeutic intervention. Cancer Immunol Res; 6(5); 578-93. ©2018 AACR.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Mediadores da Inflamação / Subunidade p50 de NF-kappa B / Inflamação Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cancer Immunol Res Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Mediadores da Inflamação / Subunidade p50 de NF-kappa B / Inflamação Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cancer Immunol Res Ano de publicação: 2018 Tipo de documento: Article