Serum amyloid P component suppresses melanoma growth and metastasis by inhibiting CCL1 secretion from macrophages

The incidence of melanoma, which is among the most common skin cancers, has significantly increased at an alarming rate over the past decade. Serum amyloid P component (SAP), a member of the pentraxin (PTX) family, is a major acute-phase protein in mice. The effects of SAP on melanoma and the mechanisms underlying these effects remain unclear. In the current study, we established xenograft and metastatic melanoma models in SAP-overexpressing (SAP-Tg) mice to determine the effect of SAP on the progression of melanoma. Compared with wild-type (WT) mice, SAP-Tg mice developed tumors with smaller volumes and fewer metastatic foci, and the degree of cell proliferation within the transplanted tumors was significantly decreased by SAP. Further study indicated that SAP inhibited melanoma growth and metastasis by suppressing CC-chemokine 1 (CCL1) secretion from activated macrophages, while CCL1 promoted the migration and invasion of B16F10 melanoma cells. Furthermore, SAP-induced CCL1 downregulation suppressed Ras/p-ERK pathway activation. These findings indicate a new effect of SAP mediated via a novel mechanism and provide direct evidence that SAP may have therapeutic value for melanoma.