Targeting Tyrosine Phosphatases by 3-Bromopyruvate Overcomes Hyperactivation of Platelets from Gastrointestinal Cancer Patients.
J Clin Med
; 8(7)2019 Jun 28.
Article
en En
| MEDLINE
| ID: mdl-31261776
ABSTRACT
Venous thromboembolism (VTE) is one of the most common causes of cancer related mortality. It has been speculated that hypercoagulation in cancer patients is triggered by direct or indirect contact of platelets with tumor cells, however the underlying molecular mechanisms involved are currently unknown. Unraveling these mechanisms may provide potential avenues for preventing platelet-tumor cell aggregation. Here, we investigated the role of protein tyrosine phosphatases in the functionality of platelets in both healthy individuals and patients with gastrointestinal cancer, and determined their use as a target to inhibit platelet hyperactivity. This is the first study to demonstrate that platelet agonists selectively activate low molecular weight protein tyrosine phosphatase (LMWPTP) and PTP1B, resulting in activation of Src, a tyrosine kinase known to contribute to several platelet functions. Furthermore, we demonstrate that these phosphatases are a target for 3-bromopyruvate (3-BP), a lactic acid analog currently investigated for its use in the treatment of various metabolic tumors. Our data indicate that 3-BP reduces Src activity, platelet aggregation, expression of platelet activation makers and platelet-tumor cell interaction. Thus, in addition to its anti-carcinogenic effects, 3-BP may also be effective in preventing platelet-tumor cell aggregationin cancer patients and therefore may reduce cancer mortality by limiting VTE in patients.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
J Clin Med
Año:
2019
Tipo del documento:
Article
País de afiliación:
Países Bajos