1. ¹Laboratory of Pathology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
2. ²Laboratory of Vaccinology and Mucosal Immunity, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
3. ³Laboratory of Molecular Bacteriology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium
4. ⁴Laboratory of Toxicology, Institute of Pharmacy, Université Libre de Bruxelles, Brussels, Belgium

Correspondence: Professor I Salmon, MD, PhD, Laboratory of Pathology, Erasme Hospital, Université Libre de Bruxelles, 808 Lennik Road, Brussels 1070, Belgium. E-mail: Isabelle.Salmon@erasme.ulb.ac.be

Received 23 October 2007; Revised 17 March 2008; Accepted 11 April 2008; Published online 9 June 2008.

Abstract

The role of tumor-associated macrophages (TAMs) is controversial. Although most studies on different cancer types associate them with a poorer prognosis, interestingly in colon cancer, most articles indicate that TAMs prevent tumor development; patients with high TAMs have better prognosis and survival rate. M1-polarized macrophages produce high level of tumor necrosis factor-, interleukin-1 or reactive oxygen species, which can effectively kill susceptible tumor cells. In contrast, M2-polarized macrophages can secrete different factors that promote tumor cell growth and survival or favor angiogenesis and tissue invasion. Considering the beneficial role of TAMs in colon cancer, we speculated that they may not display the M2 polarization commonly observed in tumor microenvironment, but rather develop M1 properties. Therefore, we used an in vitro model to analyze the effects of supernatants from M1-polarized macrophages on DLD-1 colon cancer cells. Our data indicate that the conditioned medium from LPS-activated macrophages (CM-LAM) contains a high level of granulocyte-macrophage colony-stimulating factor, interleukins-1, -6, -8 and tumor necrosis factor-, and that it exerts a marked growth inhibitory activity on DLD-1 cells. Prolonged exposure to CM-LAM results in cell death by apoptosis. Such exposure to CM-LAM leads to the modulation of gal-3 expression: we observed a marked downregulation of gal-3 mRNA and protein expression following CM-LAM treatment. We also describe that the knockdown of gal-3 sensitizes DLD-1 cells to CM-LAM. These data suggest an involvement of gal-3 in the response of colon cancer cells to proinflammatory stimuli, such as the conditioned medium from activated macrophages.