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Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres
Published on: July 22, 2020
S100A8/A9 activate key genes and pathways in colon tumor progression
Mie Ichikawa1, Roy Williams, Ling Wang
1Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, 10905 Road to the Cure, San Diego, CA 92121, USA.
Molecular Cancer Research : MCR
|January 14, 2011
Summary
Myeloid-derived S100A8/A9 proteins promote colon cancer growth and metastasis by activating tumor cells and recruiting immune cells. Deleting S100A9 significantly reduced tumor incidence, growth, and spread.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- The tumor microenvironment significantly influences cancer progression.
- S100A8/A9 proteins secreted by myeloid-derived suppressor cells (MDSC) create an autocrine pathway for MDSC accumulation.
- S100A8/A9-positive cells are found in dysplastic and adenomatous regions of colon cancer.
Purpose of the Study:
- To investigate the interaction of S100A8/A9 with colon tumor cells.
- To identify downstream genes activated by S100A8/A9.
- To elucidate the role of myeloid-derived S100A8/A9 in colon tumorigenesis and metastasis.
Main Methods:
- Analysis of S100A8/A9 interactions with RAGE and glycans on colon tumor cells.
- Gene expression profiling of S100A8/A9-activated versus unactivated colon tumor cells.
- Assessment of tumor incidence, growth, metastasis, and immune cell infiltration in wild-type and S100A9-deficient mice, including bone marrow chimeric studies.
Main Results:
- S100A8/A9 activate MAPK and NF-κB signaling pathways in colon tumor cells.
- Upregulation of genes (e.g., Cxcl1, Ccl5, Ccl7) involved in leukocyte recruitment, angiogenesis, and metastasis.
- Mice lacking S100A9 exhibited reduced tumor incidence, growth, metastasis, chemokine levels, and immune cell infiltration.
- Myeloid S100A8/A9 expression is crucial for colon tumor development.
Conclusions:
- Myeloid-derived S100A8/A9 proteins promote colon tumorigenesis and metastasis.
- S100A8/A9 activate specific downstream genes that drive tumor growth and spread.
- Targeting S100A8/A9 may offer a therapeutic strategy for colon cancer.
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