title: C-reactive protein reduces the relative number of tumor-associated M2 macrophages and intratumoral angiogenesis in mice.
abstract: Tumor-associated macrophages play a key role in cancer metastasis. On the other hand, C-reactive protein (CRP), a widely used biomarker of inflammation, has been shown to have inhibitory effects on tumor proliferation and metastasis. Here we used an implanted tumor mouse model to assess the effect of CRP on tumor-associated macrophage numbers and on their phenotype, as well as on intratumoral angiogenesis. NR-S1M murine oral squamous cell carcinoma cells were implanted subcutaneously in the backs of anesthetized C3H/HeN mice. Some of the mice were also subcutaneously administered 1 μg of recombinant mouse CRP in 100 μL of phosphate-buffered saline (PBS) (CRP group, n = 10) near the neck every 2 days for 30 days (15 injections in all). Control mice received PBS without CRP. The mice were then sacrificed and the excised tumors were analyzed. Tumor weight and size did not differ between the two groups, but immunohistochemical analysis showed the F4/80(+) macrophage (total macrophages) count to be significantly larger in the CRP group (P = 0.0028), while the relative number of CD206(+) anti-inflammatory M2 macrophages was significantly reduced (P = 0.0091). In addition, expression of colony stimulating factor 1 mRNA, which is associated with the M2 macrophage phenotype, was significantly lower in the CRP group. Intratumoral angiogenesis, indicated by the presence of CD31(+) vessels within the tumor, was reduced in the CRP group (P = 0.0028). These findings suggest that CRP has therapeutic potential against cancer through decreasing the accumulation of M2 macrophages and angiogenesis within tumors.
authors.affiliation: Department of Surgery, Akita University Graduate School of Medicine.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Kuribayashi
authors.forename: Satoru
authors.initials: S
authors.lastname: Motoyama
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Sasaki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.forename: Kei
authors.initials: K
authors.lastname: Yoshino
authors.forename: Akiyuki
authors.initials: A
authors.lastname: Wakita
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Imai
authors.forename: Hajime
authors.initials: H
authors.lastname: Saito
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Minamiya
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism*; D002452:Cell Count; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D047368:Tumor Burden
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D002097:C-Reactive Protein