It has been known for many decades now that aspirin has effects on prevention and metastasis of malignant tumors, but few are aware of this.  The strongest evidence is in Colo-Rectal Cancer.  Recently, Yang et al has clarified the mechanism and immunology.  Release of Thromboxane A2 from platelets stimulates the production of a protein in T cells called ARHGEF1, which inhibits T cell cytotoxic activity, allowing cancer cells to proliferate and metastasize.

Aspirin irreversibly blocks the Cox1 enzyme which is used in the conversion of Arachidonic Acid to Prostaglandin H2, which is a substrate that is further catalyzed by Thromboxane Synthetase to make Thromboxane A2.  Thromboxane A2 is important for causing platelet activation and platelet aggregation. 

Platelets interact with tumor cells in a variety of ways.  Tumors cells shield themselves when they enter the circulation by using platelets to form a protective shell, thus masking tumor antigens, blocking immune system cells and complement-mediated lysis.  Immune cells see this platelet-tumor complex as “self,” instead of “non-self.”  Shearing forces in the blood stream are severe but the adhered platelets serve as a buffer to cancer cells, allowing them to survive their journey through the circulation in route to metastasizing in downstream tissues.  Platelets also express adhesion molecules (to clot blood) allowing them, with the attached cancer cells, to stick to vascular endothelium and capillary beds in organs.  Platelets also modulate pro-metastatic signaling molecules such as VEGF, which stimulates angiogenesis, an essential ingredient of tumor growth and spread. Platelets also release TGF-B, which decreases cell to cell adhesion, thus increasing mobility, and enhancing tissue invasion.  TGF-B also suppresses Natural Killer Cell activity.  On top of everything else, thromboxane A2 signals T-cells to produce a protein (ARHGEF1) which inhibits cytotoxic activity.  The anti-platelet activity of Aspirin reduces all of these activities and thus reduces tumor spread.

Aspirin also inhibits Cox2 enzymes, present in most tissues, including tumor cells, which are stimulated and up regulated by Thromboxane A2 from platelets.  COX2 enzymes promote the formation of PGE2, which is upregulated in the face of inflammation and is a major oncogenic stimulator.  Chronic inflammation can lead to carcinogenesis.  Inhibiting Cox2 decreases chronic inflammation and also leads to decreased angiogenesis and tissue invasion.   The Cox2 enzyme is over-expressed in many cancers, including Colo-rectal, Breast, Lung, Pancreatic, and Prostate.

Regular use of aspirin has been associated with a reduction in colonic Adenomas, a 22 % reduction in Colo-rectal cancer, and a reduction in the risk of developing metastatic Colorectal Cancer.