Serum amyloid P down-regulates CCL-1 expression, and inhibits Ras/MAPK signaling and development of breast cancer
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
Submission of a manuscript to this journal is a representation that the manuscript has not been published previously and is not under consideration for publication elsewhere.
All authors named in each manuscript would be required to sign a form (to be supplied by the Editor) so that they may retain their copyright in the article but to assign to us (the Publishers) and its licensees in perpetuity, in all forms, formats and media (whether known or created in the future) to (i) publish, reproduce, distribute, display and store the contribution, (ii) translate the contribution into other languages, create adaptations, reprints, include within collections and create summaries, extracts and/or abstracts of the contribution, (iii) create any other derivative works(s) based on the contribution, (iv) to exploit all subsidiary rights in the contribution, (v) the inclusion of electronic links from the contribution to third party material where-ever it may be located, and (vi) license any thrid party to do any or all of the above.
