Jacalin-Activated Macrophages Exhibit an Antitumor Phenotype.

Cláudia Danella Polli,Luciana Chain Veronez,Luciana Pereira Ruas,Thais Herrero Geraldino,Maria Cristina Roque-Barreira,Gabriela Pereira-Da-Silva,Fabiana Rossetto De Morais

doi:10.1155/2016/2925657

Abstract

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.

Highlights

IntroductionBesides the tumor cells, of a wide population of leukocytes and other types of infiltrating immune cells [1]
Tumors are composed, besides the tumor cells, of a wide population of leukocytes and other types of infiltrating immune cells [1]
We analyzed the modulation of macrophage tumoricidal activities against human colon (HT29) and breast (MCF-7) adenocarcinoma cells by the lectin jacalin

Summary

Introduction

Besides the tumor cells, of a wide population of leukocytes and other types of infiltrating immune cells [1]. Tumorassociated macrophages (TAMs) constitute a key component of the leukocytic infiltrate in tumors [3] and can exert different properties depending on the microenvironment. These cells act as fundamental inflammatory orchestrators in the development of different types of tumors. Microbicidal and tumoricidal M1 macrophages are induced by IFN-γ alone or in concert with microbial stimuli, such as LPS or cytokines (e.g., TNF-α). These cells secrete high levels of proinflammatory cytokines (e.g., TNFα, IL-12, IL-23, IL-6, and IL1-β), chemokines, and effector molecules, such as inducible nitric oxide synthase (iNOS) and MHCI/II. Given that TAMs can respond to different signals from the tumor microenvironment, there has been considerable effort to develop immunotherapies that skew their behavior to become cancer-suppressive

Methods

Results

Conclusion