Abstract
Background: Colorectal cancer (CRC) is the third most common and the fourth most deadly cancer and inflammation contributes to CRC development. Thus, targeting inflammatory cells and mediators can potentially reduce the development, growth and spread of disease. Mast cells accumulate in CRC tissues and can play a dual role in the development of cancer. They can inhibit tumor growth through the cytotoxic activity of released proteases, but they also promote tumor growth via the release of growth factors and angio-genic factors, and cause suppression of a protective immune response. Mast cell density is correlated to tumor progression and clinical outcome in patients with CRC. In this study, we provide further insight into the effects of human mast cells (HMC) and their mediators on the progression of colon cancer growth. Method: CD34+-derived HMC were generated and their interaction with human colon cancer cell lines (HT29 and Caco2) was investigated in both 2D and 3D co-culture models. Transwell assays were used to analyze HMC chemotaxis to colon cancer and BrdU proliferation assays were used to study the effect of HMC on colon cancer proliferation. 3D cancer spheroid models with HMC and HT29 colon cancer cells were established to explore the relationship of HMC and colon cancer growth and invasion, which was visualized by con-focal microscopy. Results: HT29 and Caco2 colon cancer cells induced HMC migration via the release of CCL15 and SCF, respectively. HMC promoted colon cancer proliferation and this effect depended on the bidirectional crosstalk between HMC and colon cancer cells. 3D cancer spheroid models showed this crosstalk was possibly mediated via soluble mediators. Furthermore, TLR2-stimulated HMC induced a stronger growth of colon cancer compared with non-stimulated HMC, as indicated by spheroid area (0.23 ± 0.05 mm2 vs 0.34 ± 0.12 mm2). Conclusion: Collectively, in this study for the first time a 3D co-culture model of primary HMC and human colon cancer cells is established, which provides an advanced in vitro model to investigate the molecular mechanism of mast cell-colon cancer interaction. The results from this study indicate that a bidirectional crosstalk is responsible for HMC recruitment and enhanced colon cancer growth.
Original language | English |
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Pages | 266 |
Number of pages | 1 |
DOIs | |
Publication status | Published - Aug 2018 |
Event | European Academy of Allergy and Clinical Immunology Congress - Munich, Germany Duration: 26 May 2018 → 30 May 2018 |
Conference
Conference | European Academy of Allergy and Clinical Immunology Congress |
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Country/Territory | Germany |
City | Munich |
Period | 26/05/18 → 30/05/18 |
Keywords
- CD34 antigen
- endogenous compound
- growth factor
- proteinase
- toll like receptor 2
- adult
- advanced cancer
- BrdU assay
- cancer growth
- cancer patient
- cell density
- cell migration
- chemotaxis
- clinical article
- clinical outcome
- coculture
- colon cancer cell line
- colorectal cancer
- conference abstract
- controlled study
- cytotoxicity
- female
- filters and membranes
- HT-29 cell line
- human
- human cell
- human tissue
- immune response
- male
- mast cell
- mediator
- microscopy
- oncology
- outcome assessment
- tumor growth