Serum amyloid P down-regulates CCL-1 expression, and inhibits Ras/MAPK signaling and development of breast cancer

  • Shuhong Ding
  • Hongzhi Li
  • Xiaohui Li
  • Wenwen Wang
  • Xiuling Du
  • Guoying Dong
  • Ping Zhang
Keywords: Serum amyloid component P (SAP), chemokine (CC motif) ligand 1 (CCL-1), Breast cancer, NF-κB, Ras/MAPK signaling pathway

Abstract

Purpose: To investigate the role of serum amyloid component P (SAP) on Ras/MAPK pathway in the development of breast cancer (BC) via regulation of chemokine (CC motif) ligand 1 (CCL-1).

Methods: Breast cancer (BC) and metastasis models were established using SAP-Tg transgenic mice and WT C57BL/6 mice. The effect of SAP on growth and metastasis was observed. Differentially expressed proteins in SAP-Tg and C57BL/6 serum were analyzed, and further determined by enzymelinked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (qPCR). The effect of SAP on CCL1/Ras/MAPK signaling pathway was studied by immunoblotting.

Results: Compared with WT control, SAP-Tg BC model showed a significant reduction in tumor volume and prolonged survival (p < 0.05). In the lung metastasis model, SAP-Tg mice showed a decreased number of nodules on the organ surface (p < 0.05). Protein microarray screening results showed that SAP inhibited CCL-1 expression (p < 0.05). CCL-1 mRNA level in SAP-Tg mice was significantly lower than WT control (p < 0.05). After stimulating RAW cells (mouse macrophage line) with SAP recombinant protein, ELISA results showed that CCL-1 secretion significantly decreased (p < 0.05). In both models, P38 and ERK1/2 activation in SAP-Tg mice were significantly lower than that in C57BL/6 mice.

Conclusion: SAP inhibits the growth and metastasis of BC, possibly by reducing the secretion of CCL- 1 and inhibiting Ras/MAPK signaling pathway, thus suggesting a possible treatment strategy for breast cancer.

Keywords: Serum amyloid component P (SAP), chemokine (CC motif) ligand 1 (CCL-1), Breast cancer, NF-κB, Ras/MAPK signaling pathway

Published
2017-10-04
Section
Articles

Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996