Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 104, Issue 4, Pages 1311-1323Publisher
WILEY
DOI: 10.1002/jcb.21709
Keywords
ADPase; aspirin; bone metastasis; platelets
Categories
Funding
- NCI NIH HHS [R01 CA097250, P50 CA94056, R01 CA097250-01A1, P50 CA094056, R01-CA097250] Funding Source: Medline
- NHLBI NIH HHS [5-T32-HL07088-32, T32 HL007088] Funding Source: Medline
- NIGMS NIH HHS [5-T32-GM-07200, T32 GM007200] Funding Source: Medline
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Platelets contribute to the development of metastasis, the most common cause of mortality in cancer patients, but the precise role that anti-platelet drugs play in cancer treatment is not defined. Metastatic tumor cells can produce platelet alpha IIb beta 3 activators, such as ADP and thromboxane A(2) (TXA(2)). Inhibitors of platelet beta 3 integrins decrease bone metastases in mice but are associated with significant bleeding. We examined the role of a novel soluble apyrase/ADPase, APT102, and an inhibitor of TXA2 synthesis, acetylsalicylic acid (aspirin or ASA), in mouse models of experimental bone metastases. We found that treatment with ASA and APT102 in combination (ASA+ APT102), but not either drug alone, significantly decreased breast cancer and melanoma bone metastases in mice with fewer bleeding complications than observed with alpha IIb beta 3 inhibition. ASA+APT102 diminished tumor cell induced platelet aggregation but did not directly alter tumor cell viability. Notably, APT102 + ASA treatment did not affect initial tumor cell distribution and similar results were observed in beta 3-/- mice. These results show that treatment with ASA + APT102 decreases bone metastases without significant bleeding complications. Anti-platelet drugs such as ASA+APT102 could be valuable experimental tools for studying the role of platelet activation in metastasis as well as a therapeutic option for the prevention of bone metastases.
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