Interaction between Tumor-Associated Dendritic Cells and Colon Cancer Cells Contributes to Tumor Progression via CXCL1.

Abstract

Crosstalk of a tumor with its microenvironment is a critical factor contributing to cancer development. This study investigates the soluble factors released by tumor-associated dendritic cells (TADCs) responsible for increasing cancer stem cell (CSC) properties, cell mobility, and epithelial-to-mesenchymal transition (EMT). Dendritic cells (DCs) of colon cancer patients were collected for phenotype and CXCL1 expression by flow cytometry and Luminex assays. The transcriptome of CXCL1-treated cancer cells was established by next generation sequencing. Inflammatory chemokine CXCL1, present in large amounts in DCs isolated from colon cancer patients, and SW620-conditioned TADCs, enhance CSC characteristics in cancer, supported by enhanced anchorage-independent growth, CD133 expression and aldehyde dehydrogenase activity. Additionally, CXCL1 increases the metastatic ability of a cancer by enhancing cell migration, matrix metalloproteinase-7 expression and EMT. The enhanced CXCL1 expression in DCs is also noted in mice transplanted with colon cancer cells. Transcriptome analysis of CXCL1-treated SW620 cells indicates that CXCL1 increases potential oncogene expression in colon cancer, including PTHLH, TYRP1, FOXO1, TCF4 and ZNF880. Concurrently, CXCL1 displays a specific microRNA (miR) upregulated by the prototypical colon cancer onco-miR miR-105. Analysis of publicly available data reveals CXCL1-driven oncogenes and miR-105 have a negative prognostic impact on the outcome of colon cancer. This study indicates a new mechanism by which the colon cancer milieu exploits DC plasticity to support cancer progression.

• Authors: Ya-Ling Hsu, Yi-Jen Chen, Wei-An Chang, Shu-Fang Jian, Hsiao-Li Fan, Jaw-Yuan Wang, Po-Lin Kuo
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 19 Issue 8 (Aug 16 2018) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 30115896 (Publication Type: Journal Article)

Chemical References

• CXCL1 protein, human
• Chemokine CXCL1

Topics

• Animals
• Cell Line, Tumor
• Cell Movement (genetics)
• Chemokine CXCL1 (genetics, metabolism)
• Colonic Neoplasms (genetics, pathology)
• Dendritic Cells (metabolism, pathology)
• Disease Progression
• Epithelial-Mesenchymal Transition (genetics)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Mice, Inbred BALB C
• Models, Biological
• Neoplastic Stem Cells (metabolism, pathology)
• Phenotype
• Transcriptome (genetics)
• Treatment Outcome
• Up-Regulation (genetics)