APT102, a novel adpase, cooperates with aspirin to disrupt bone metastasis in mice.
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 alphaIIb beta3 activators, such as ADP and thromboxane A(2) (TXA(2)). Inhibitors of platelet beta3 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 TXA(2) 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 alphaIIb beta3 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 beta3-/- 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.
Uluçkan
Ozge
O
Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Eagleton
Mark C
MC
Floyd
Desiree H
DH
Morgan
Elizabeth A
EA
Hirbe
Angela C
AC
Kramer
Matthew
M
Dowland
Nikki
N
Prior
Julie L
JL
Piwnica-Worms
David
D
Jeong
Soon Seog
SS
Chen
Ridong
R
Weilbaecher
Katherine
K
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D001081:Apyrase / Q000494:pharmacology / Q000627:therapeutic use*; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D003952:Diagnostic Imaging; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D047368:Tumor Burden / Q000187:drug effects
D010975:Platelet Aggregation Inhibitors; D001081:Apyrase; D001241:Aspirin