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Evidence that aspirin blocks platelet‐induced growth, invasive activity and epithelial‐mesenchymal‐transition (EMT) of mouse colon cancer cells
Author(s) -
Lichtenberger Lenard M,
Fang Dexing,
Dial Elizabeth,
Vijayan K. Vinod
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.937.4
Subject(s) - aspirin , platelet , colorectal cancer , medicine , matrigel , cancer research , cell growth , cancer , platelet activation , cancer cell , chemistry , angiogenesis , biochemistry
Background Aspirin consumption is associated with a significant reduction in the incidence and mortality of colorectal cancer (CRC). The evidence was sufficiently compelling to lead a subcommittee of the US Preventive Services Task Force (USPSTF) this year to recommend that individuals aged 50–69 years of age take low‐dose aspirin for chemoprevention of CRC. There is also evidence that platelet number is increased in late‐stage cancer patients and that platelets may stimulate cancer cell growth and EMT. Objective To determine if aspirin's chemopreventive action against CRC may be due to the drugs ability to inhibit platelet activation (via irreversible COX‐1 acetylation) and thereby block platelet‐ induced effects on CRC cell growth, invasive activity and EMT. Methods MC‐26 mouse colon cancer cells were incubated in cell culture on Transwell plates in the absence and presence of freshly isolated mouse platelets, at a cell : platelet ratio of 1:400 and 1:800, in medium containing aspirin from 0–1mM. Cell growth, invasive activity (translocation across the Matrigel‐coated membrane insert), and EMT (change in cell shape, and β‐catenin nuclear translocation) were assessed at different periods of culture. Medium Thromboxane B 2 (TXB 2 ) conc was measured by ELISA. Results Co‐culture of colon cancer cells with platelets induced a significant increase in MC‐26 cell number and invasive activity and an activation of EMT, as the cells transformed from an epithelial to a mesenchymal shape with the generation of intracellular and extracellular microfilaments and an increase in medium TXB 2 conc. Aspirin at concentrations between 0.3–1.0 mM blocked platelet activation (as indicated by a >95% reduction in medium TXB 2 ) and all of the above dysplastic platelet‐induced changes in the colon cancer cells in culture. Conclusion Aspirin's chemopreventive action against colon cancer may be dependent on the drug's ability to irreversibly block platelet activation and the ability of platelets to promote cancer cell growth, invasion and EMT. Support or Funding Information Supported by NIH grant R21 CA182798.