Abstract
Background and ObjectiveS100A8 and S100A9, two members of the S100 protein family, have been reported in association with the tumor cell differentiation and tumor progression. Previous study has showed that their expression in stromal cells of colorectal carcinoma (CRC) is associated with tumor size. Here, we investigated the clinical significances of S100A8 and S100A9 in tumor cells of CRC and their underlying molecular mechanisms.MethodsExpression of S100A8 and S100A9 in colorectal carcinoma and matching distal normal tissues were measured by reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry and western blot. CRC cell lines treated with the recombinant S100A8 and S100A9 proteins were used to analyze the roles and molecular mechanisms of the two proteins in CRC in vitro.ResultsS100A8 and S100A9 were elevated in more than 50% of CRC tissues and their expression in tumor cells was associated with differentiation, Dukes stage and lymph node metastasis. The CRC cell lines treatment with recombinant S100A8 and S100A9 proteins promoted the viability and migration of CRC cells. Furthermore, the two recombinant proteins also resulted in the increased levels of β-catenin and its target genes c-myc and MMP7. β-catenin over-expression in CRC cells by Adβ-catenin increased cell viability and migration. β-catenin knock-down by Adsiβ-catenin reduced cell viability and migration. Furthermore, β-catenin knockdown also partially abolished the promotive effects of recombinant S100A8 and S100A9 proteins on the viability and migration of CRC cells.ConclusionsOur work demonstrated that S100A8 and S100A9 are linked to the CRC progression, and one of the underlying molecular mechanisms is that extracellular S100A8 and S100A9 proteins contribute to colorectal carcinoma cell survival and migration via Wnt/β-catenin pathway.
Highlights
Colorectal carcinoma (CRC) is the third leading cause of cancer-associated death worldwide
We found that S100A8 and S100A9 were elevated in CRC, and their expression in tumor cells was associated with the differentiation, Dukes stage and lymph node metastasis
We found that the recombinant S100A8 and S100A9 proteins promote the viability and migration of CRC cells and upregulate the activity of Wnt/bcatenin pathway, and that their effect on cell viability and migration was partially mediated by upregulating Wnt/b-catenin pathway
Summary
Colorectal carcinoma (CRC) is the third leading cause of cancer-associated death worldwide. In recent years, understanding the cancer-specific genes and potential molecular mechanisms during the carcinogenesis and progression of CRC provides an opportunity for the development of targeted therapy for the treatment of CRC. The over-expression of S100A8 and S100A9 has been observed in many tumor cells, and is associated with poor cell differentiation in some cancers of glandular cell origin [6,7,8,9]. It is reported that expression of S100A8 or S100A9 in stromal cells of CRC is associated with larger-sized tumors [11]. S100A8 and S100A9, two members of the S100 protein family, have been reported in association with the tumor cell differentiation and tumor progression. Previous study has showed that their expression in stromal cells of colorectal carcinoma (CRC) is associated with tumor size. We investigated the clinical significances of S100A8 and S100A9 in tumor cells of CRC and their underlying molecular mechanisms
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