Targeting Tyrosine Phosphatases by 3-Bromopyruvate Overcomes Hyperactivation of Platelets from Gastrointestinal Cancer Patients

Autor(es)

Faria, Alessandra V. S. ^{[1, 2]} ; Andrade, Sheila S. ^[3] ; Reijm, Agnes N. ^[1] ; Spaander, Manon C. W. ^[1] ; de Maat, Moniek P. M. ^[4] ; Peppelenbosch, Maikel P. ^[1] ; Ferreira-Halder, V, Carmen ; Fuhler, Gwenny M. ^[1]

Afiliação do(s) autor(es)

^[1] Erasmus MC, Dept Gastroenterol & Hepatol, NL-3000 CA Rotterdam - Netherlands

^[2] V, Univ Estadual Campinas, Dept Biochem & Tissue Biol, UNICAMP, BR-13083862 Campinas, SP - Brazil

^[3] PlateInnove Biotechnol, BR-13414018 Piracicaba, SP - Brazil

^[4] Erasmus MC, Dept Hematol, NL-3000 CA Rotterdam - Netherlands

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF CLINICAL MEDICINE; v. 8, n. 7 JUL 2019.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 17/08119-8 - Primeira etapa da disseminação hematogênica de células de câncer de cólon retal: influência da LMWPTP e do 3-bromopiruvato
• Beneficiário: Alessandra Valéria de Sousa Faria
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/00736-0 - Correlação de microRNA em amostras de fezes e plaquetas de pacientes com câncer gastrointestinal e proteína tirosina fosfatase ACP1: triagem em câncer coloretal
• Beneficiário: Alessandra Valéria de Sousa Faria
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 15/20412-7 - Proteína tirosina fosfatase de baixo peso molecular em câncer de cólon retal: da bancada à geração de produto
• Beneficiário: Carmen Veríssima Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático