title: C-reactive protein inhibits lymphangiogenesis and resultant lymph node metastasis of squamous cell carcinoma in mice.
abstract: BACKGROUND
  Lymph node involvement is the most important prognostic factor in many solid cancers. Recently, we found that patients with esophageal and lung cancer carrying the C-reactive protein (CRP) 1846T/T genotype, which is associated with lower serum CRP levels, are more likely to have lymph node metastasis. We hypothesized that host CRP directly inhibits lymph node metastasis.
  
  
  METHODS
  We inoculated NR-S1M metastatic cells subcutaneously into the backs of C3H/HeN mice. Concurrently, 1 μg of recombinant mouse CRP or phosphate-buffered saline was injected subcutaneously every 3 days for 5 weeks, after which the mice were killed for evaluation. We evaluated lymph node metastasis and lymphangiogenesis in the implanted tumor by using immunohistochemical analysis with anti-pancytokeratin and antilymphatic vessel endothelial hyaluronan receptor-1 antibodies.
  
  
  RESULTS
  There was no substantial difference in tumor size between the 2 groups but the lymph nodes were smaller in the CRP group than the control group (P < .044). Immunohistochemical analysis confirmed inguinal lymph node metastasis in 70% (14/20) of control mice, but in only 30% (3/10) of mice in the CRP group. Moreover, the metastatic area within lymph nodes was less in the CRP group (P < .042) and tumoral lymphangiogenesis was decreased in the CRP group (P < .037).
  
  
  CONCLUSIONS
  CRP appears to inhibit tumoral lymphangiogenesis and lymph node metastasis in mice. These findings suggest that by inhibiting lymph node metastasis, CPR may have therapeutic potential for use against cancer.
authors.affiliation: Department of Surgery, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Sasaki
authors.forename: Satoru
authors.initials: S
authors.lastname: Motoyama
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.forename: Kei
authors.initials: K
authors.lastname: Yoshino
authors.forename: Goichi
authors.initials: G
authors.lastname: Matsumoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Minamiya
authors.forename: Hajime
authors.initials: H
authors.lastname: Saito
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Murata
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000502:physiology* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D045744:Cell Line, Tumor; D005260:Female; D008198:Lymph Nodes / Q000473:pathology; D042583:Lymphangiogenesis / Q000502:physiology*; D008207:Lymphatic Metastasis / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D051379:Mice; D008809:Mice, Inbred C3H
chemical_list: D002097:C-Reactive Protein