Jacalin-Activated Macrophages Exhibit an Antitumor Phenotype.
Tumor-associated macrophages (TAMs) have an ambiguous and complex role in the carcinogenic process, since these cells can be polarized into different phenotypes (proinflammatory, antitumor cells or anti-inflammatory, protumor cells) by the tumor microenvironment. Given that the interactions between tumor cells and TAMs involve several players, a better understanding of the function and regulation of TAMs is crucial to interfere with their differentiation in attempts to skew TAM polarization into cells with a proinflammatory antitumor phenotype. In this study, we investigated the modulation of macrophage tumoricidal activities by the lectin jacalin. Jacalin bound to macrophage surface and induced the expression and/or release of mainly proinflammatory cytokines via NF-κB signaling, as well as increased iNOS mRNA expression, suggesting that the lectin polarizes macrophages toward the antitumor phenotype. Therefore, tumoricidal activities of jacalin-stimulated macrophages were evaluated. High rates of tumor cell (human colon, HT-29, and breast, MCF-7, cells) apoptosis were observed upon incubation with supernatants from jacalin-stimulated macrophages. Taken together, these results indicate that jacalin, by exerting a proinflammatory activity, can direct macrophages to an antitumor phenotype. Deep knowledge of the regulation of TAM functions is essential for the development of innovative anticancer strategies.
Programa de Pós-Graduação em Imunologia Básica e Aplicada, FMRP/USP, 14049-900 Ribeirão Preto, SP, Brazil.
Cláudia
C
Danella Polli
Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, FMRP/USP, 14049-900 Ribeirão Preto, SP, Brazil.
Luciana
L
Pereira Ruas
Programa de Pós-Graduação em Imunologia Básica e Aplicada, FMRP/USP, 14049-900 Ribeirão Preto, SP, Brazil.
Luciana
L
Chain Veronez
Programa de Pós-Graduação em Imunologia Básica e Aplicada, FMRP/USP, 14049-900 Ribeirão Preto, SP, Brazil.
Thais
T
Herrero Geraldino
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, FCFRP/USP, 14040-903 Ribeirão Preto, SP, Brazil.
Fabiana
F
Rossetto de Morais
Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, FMRP/USP, 14049-900 Ribeirão Preto, SP, Brazil.
Maria Cristina
MC
Roque-Barreira
Departamento de Enfermagem Materno-Infantil e Saúde Pública, EERP/USP, 14040-902 Ribeirão Preto, SP, Brazil.
Gabriela
G
Pereira-da-Silva
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D061986:MCF-7 Cells; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D037121:Plant Lectins / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects / Q000235:genetics
D016328:NF-kappa B; D037121:Plant Lectins; D012333:RNA, Messenger; C043696:jacalin; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II