title: Galectin-3 accelerates M2 macrophage infiltration and angiogenesis in tumors.
abstract: It is widely accepted that robust invasion of tumor-associated macrophages resembling M2 macrophage correlates with disease aggressiveness by affecting cancer cell invasion, metastasis, and angiogenesis. Many chemokines that induce migration of macrophages have been identified during inflammatory responses; however, further precise analysis of macrophage migration in the tumor microenvironment is required. Here, we analyzed the function of galectin-3 (Gal-3; gene LGALS3, alias Gal3) for macrophage chemotaxis using Gal3(-/-) mice as hosts, and a tumor allograft model. We engineered a concentration gradient of Gal-3 produced by the tumor. In this model, we found that macrophage infiltration was enhanced in tumors developing in these Gal3(-/-) mice relative to the Gal3(+/+) animals. This was accompanied by enhanced tumor angiogenesis and tumor growth in Gal3(-/-) mice. We found that macrophages of the M2 phenotype were dominant in infiltrates in the Gal3(-/-) mice and that they expressed only low levels of Gal-3. Gal3 knockdown by siRNA in macrophages resulted in enhanced chemotaxis. These data suggest that M2-like macrophages migrate into the tumor along a Gal-3 gradient and that high-level Gal-3 expression in the tumor results in acceleration of angiogenesis and tumor growth. Therefore, Gal-3 could be a potential target for the development of new treatments to inhibit tumor growth.
authors.affiliation: Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Weizhen
authors.initials: W
authors.lastname: Jia
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kidoya
authors.forename: Daishi
authors.initials: D
authors.lastname: Yamakawa
authors.forename: Hisamichi
authors.initials: H
authors.lastname: Naito
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takakura
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D037502:Galectin 3 / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology*
chemical_list: D037502:Galectin 3