Expression of galectin-3 in the tumor immune response in colon cancer

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-a, interleukin-1b 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-1b, -6, -8 and tumor necrosis factor-a, 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.

Transient silencing of galectin-3 expression promotes both in vitro and in vivo drug-induced apoptosis of human pancreatic carcinoma cells

“…A notable finding of the present study was that transient depletion of gal-3 by local injection of siRNA interference resulted in a significant delay in tumor growth in GEMtreated nude mice in vivo. Gal-3 has been reported to induce the proliferation of cancer cells in vitro [30][31][32][33][34][35], and gal-3 knock-down may thus affect pancreatic cancer cell growth in vivo. However, Ki-67 expression in gal-3-silenced tumors was similar to that in control tumor cells after GEM treatment, and an in vitro cell proliferation assay showed that gal-3 gene silencing had no effect on cell proliferation in pancreatic cancer cell lines at 24, 48, and 72 h (data not shown).…”

Role of lipoxins, resolvins, and other bioactive lipids in colon and pancreatic cancer

“…Blocking PAF-R would lead to the reduced levels of PGE 2 , NO, and VEGF in the tumor microenvironment. Indeed, the activation of macrophage PAF-R plays a role in macrophage-derived angiogenesis [136]. Since macrophages/dendritic cells are central actors in the maintenance of both normal and tumor tissue homeostasis, novel pharmacological interventions that may control their functions are warranted.…”

GAL3 Protein Expression is Related to Clinical Features of Prolactin-Secreting Pituitary Microadenoma and Predicts its Recurrence after Surgical Treatment

“…The expression of Gal-3 has been considered as a potential diagnostic and/or prognostic marker in stomach, colon-rectum, parathyroid, thyroid, breast, salivary glands, bladder, head and neck, prostate, and liver cancers [3,4,5,6,7,8]. Increasing evidence has revealed that Gal-3 protein plays an important role in pituitary tumorigenesis [9].…”