C-reactive protein inhibits lymphangiogenesis and resultant lymph node metastasis of squamous cell carcinoma in mice

BackgroundLymph 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.MethodsWe 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.ResultsThere 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).ConclusionCRP 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.