title: Tumor infiltrating macrophages reduce development of peritoneal colorectal carcinoma metastases.
abstract: Macrophages generally constitute a major component of tumor stroma, and possess either tumor growth promoting or inhibiting capabilities. Classically activated macrophages exert cytotoxicity and produce inflammatory cytokines, which limits tumor growth. By contrast, alternatively activated or M2 macrophages induce tumor progression by stimulating angiogenesis and proliferation. Previously we showed that resident macrophages control metastatic spread of coloncarcinoma cells in liver and peritoneal tumor models. However, it is proposed that newly recruited macrophages develop into tumor-associated M2 macrophages, as they are exposed to a microenvironment that favors alternative activation. Previously we showed that monocyte migration was diminished after flavonoid treatment in an experimental autoimmune encephalomyelitis animal model. In the present study, we investigated the role of newly recruited macrophages in colon carcinoma development, by using the flavonoids rutin and luteolin to reduce monocyte migration into peritoneal tumors. Increased tumor development was observed in animals that were treated with rutin and luteolin. Immunohistochemical analyses showed that the number of ED2(+) resident macrophages was normal in tumors of animals that received rutin and luteolin treatment. However, the number of ED1(+) cells (marker immature macrophages) was reduced, indicating decreased macrophage recruitment. Thus, inhibition of monocyte migration promotes tumor growth, supporting that not only resident, but also newly recruited macrophages limit peritoneal colon carcinoma metastases development.
authors.affiliation: Department of Surgical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Gerben J
authors.initials: GJ
authors.lastname: van der Bij
authors.forename: Marijn
authors.initials: M
authors.lastname: Bögels
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Oosterling
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kroon
authors.forename: Dénise T M
authors.initials: DT
authors.lastname: Schuckmann
authors.forename: Helga E
authors.initials: HE
authors.lastname: de Vries
authors.forename: Sybren
authors.initials: S
authors.lastname: Meijer
authors.forename: Robert H J
authors.initials: RH
authors.lastname: Beelen
authors.forename: Marjolein
authors.initials: M
authors.lastname: van Egmond
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology*; D047311:Luteolin / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D010534:Peritoneal Neoplasms / Q000556:secondary*; D051381:Rats; D011919:Rats, Inbred Strains; D012431:Rutin / Q000494:pharmacology; D017154:Stromal Cells; D059016:Tumor Microenvironment
chemical_list: D012431:Rutin; D047311:Luteolin