Interaction between Tumor-Associated Dendritic Cells and Colon Cancer Cells Contributes to Tumor Progression via CXCL1.
Ya-Ling HsuYi-Jen ChenWei-An ChangShu-Fang JianHsiao-Li FanJaw-Yuan WangPo-Lin KuoPublished in: International journal of molecular sciences (2018)
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.
Keyphrases
- dendritic cells
- poor prognosis
- long non coding rna
- papillary thyroid
- cell proliferation
- immune response
- squamous cell
- flow cytometry
- regulatory t cells
- long noncoding rna
- single cell
- epithelial mesenchymal transition
- cell migration
- squamous cell carcinoma
- small cell lung cancer
- type diabetes
- gene expression
- mesenchymal stem cells
- binding protein
- induced apoptosis
- rna seq
- oxidative stress
- cell therapy
- young adults
- climate change
- high throughput
- risk assessment
- transcription factor
- endoplasmic reticulum stress
- genome wide
- big data
- newly diagnosed
- childhood cancer