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Hematogenous tumor metastasis in colon rectal cancer cells: influence of LMWPTP and 3-bromopyruvate

Grant number: 17/08119-8
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2017
Effective date (End): August 31, 2020
Field of knowledge:Biological Sciences - Biochemistry - Enzymology
Principal researcher:Carmen Veríssima Ferreira
Grantee:Alessandra Valéria de Sousa Faria
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:15/20412-7 - Low molecular weight protein tyrosine phosphatase in colorectal cancer: from the bench to product generation, AP.TEM
Associated scholarship(s):18/00736-0 - MicroRNAs in stool and platelets biology from gastroenterology cancer patient samples that correlate with ACP1 protein tyrosine phosphatase: colorectal cancer screening, BE.EP.DR

Abstract

Despite the great progress in the development of cancer treatment protocols, the effectiveness of the therapy of several tumors is still a challenge, especially in metastatic cases. Over the last decade, our research group has explored signal transduction pathways for the understanding of tumor biology. Our studies are focused on the mechanisms and identification of molecular targets envisaging the decrease of the aggressiveness and resistance of tumor cells. Low Molecular Weight Protein Phosphatase Phosphatase (LMWPTP) is one of the potential targets described by our group, and we describe it as an important protein involved in tumor chemotherapic resistance and metastatic processes, including rectal cancer (CRC). However, specifically in the case of the metastatic process, the role of this phosphatase still needs to be clarified. Thus, the present project aims to evaluate if LMWPTP contributes to the hematogenic dissemination of CRC cells, focusing on the first phase of this process, which requires the interaction of tumor cells with platelets. For this, CRC cell lines with different levels of LMWPTP expression will be employed and the influence of the culture medium derived from the cells on the platelet function will be analyzed. In addition, we will evaluate if the level of intracellular LMWPTP correlates with a greater capacity of CRC-platelets interaction. Since the ability of platelet aggregation can correlate with the metastatic potential of the tumor, we show that the 3BP decrease the platelet function collagen-induced at health patients' samples (data at rebuttal letter). And we will proceed to show 3BP inhibition of platelet function mechanism by a) evaluation of the 3BP effect at platelet aggregation by agonists, at aggregometer; b) investigation of 3BP signaling pathways' modulation at platelet function; c) investigation of platelet aggregation induced by CRC cells with different LMWPTP expression; d) evaluation of CRC hematogenous tumor metastasis inhibition by 3BP using strategies for coculture system between platelet and CRC cells, and signaling pathways modulated by this interaction. Beyond that, this project will promote innovation by evaluating the 3BP mechanism of action at platelet function and the CRC hematogenous tumor metastasis inhibition. Overall, identify the LMWPTP role at metastatic potential by investigation of the effective interaction between of CRC cells and platelets and the contribution of metabolic pathways related to this phenomenon.

News published in Agência FAPESP Newsletter about the scholarship:
Científicos estudian la utilización de una enzima de las células tumorales para monitorear el cáncer 
Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment 
Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer 
Articles published in other media outlets (41 total):
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UOL: Enzima abundante em células tumorais poderá monitorar tratamento do câncer (11/Nov/2020)
Al Día (Cuba): Una enzima de las células tumorales puede ayudar a monitorear el cáncer (01/May/2021)
Wenku.baidu.com (China): 科学家研究了肿瘤细胞中丰富酶的使用以监测癌症的治疗 - Cientistas estudaram o uso de enzimas abundantes em células tumorais para monitorar o tratamento do câncer (14/Apr/2021)
wfn360: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (22/Jan/2021)
Programa InfoSalud (Argentina): Científicos estudian la utilización de una enzima de las células tumorales para monitorear el cáncer (14/Jan/2021)
News Medical (Austrália): Researchers investigate protein phosphatase to identify new treatments for cancer, other diseases (13/Jan/2021)
Faculty of Medicine: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (13/Jan/2021)
Sound Health and Lasting Wealth (Nigéria): Researchers investigate protein phosphatase to identify new treatments for cancer, other diseases (13/Jan/2021)
AZo Life Sciences: Protein phosphatase inhibition could contribute to the treatment of cancer, other diseases (13/Jan/2021)
Knowledia (França): Researchers investigate protein phosphatase to identify new treatments for cancer, other diseases (13/Jan/2021)
Vectors Journal: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (13/Jan/2021)
Globe Health News: Researchers investigate protein phosphatase to identify new treatments for cancer, other diseases (13/Jan/2021)
Xoonews: Researchers investigate protein phosphatase to identify new treatments for cancer, other diseases (13/Jan/2021)
Your Mag: Researchers investigate protein phosphatase to identify new treatments for cancer, other diseases (13/Jan/2021)
Sciencty: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (13/Jan/2021)
Medical Xpress (Reino Unido): Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Bioengineer (Reino Unido): Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Science Codex: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Life Extension Advocacy Foundation (EUA): Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Technology Networks (Reino Unido): Enzyme in Tumor Cells Could Be Used To Monitor Cancer Treatment (12/Jan/2021)
Scienmag Science Magazine (Reino Unido): Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Brightsurf: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
7thSpace: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Science News Net: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Ardrossan & Saltcoats Herald (Reino Unido): Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Today News Post (EUA): Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Amis-childrenshome: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
WorldNewsEra (EUA): Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
The Uncover Reality (Índia): Scientists Study Use of Abundant Enzyme in Tumor Cells to Monitor Cancer Treatment (Medicine) (12/Jan/2021)
Your Mag: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Love Avia for latest news and articles (EUA): Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Virtual Medico: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Pfarma: Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer (26/Nov/2020)
Plantão News (MT): Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer (15/Nov/2020)
NewsLab online: Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer (13/Nov/2020)
UNICAMP - Universidade Estadual de Campinas: Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer (11/Nov/2020)
LabNetwork: Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer (11/Nov/2020)
Jornal Voz da Comunidade: Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer (11/Nov/2020)
Tá Sabendo?: Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer (11/Nov/2020)
ABIPTI - Associação Brasileira das Instituições de Pesquisa Tecnológica e Inovação: Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer (11/Nov/2020)
Digital Rádio e TV: Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer (11/Nov/2020)

Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FARIA, ALESSANDRA V. S.; ANDRADE, SHEILA S.; PEPPELENBOSCH, MAIKEL P.; FERREIRA-HALDER, V, CARMEN; FUHLER, GWENNY M. The role of phospho-tyrosine signaling in platelet biology and hemostasis. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1868, n. 3 MAR 2021. Web of Science Citations: 0.
FARIA, ALESSANDRA V. S.; ANDRADE, SHEILA S.; PEPPELENBOSCH, MAIKEL P.; FERREIRA-HALDER, CARMEN V.; FUHLER, GWENNY M. Platelets in aging and cancer-{''}double-edged sword{''}. CANCER AND METASTASIS REVIEWS, v. 39, n. 4, SI SEP 2020. Web of Science Citations: 0.
CORDEIRO, HELON GUIMARAES; DE SOUSA FARIA, ALESSANDRA VALERIA; FERREIRA-HALDER, CARMEN VERISSIMA. Vemurafenib downmodulates aggressiveness mediators of colorectal cancer (CRC): Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP), Protein Tyrosine Phosphatase 1B (PTP1B) and Transforming Growth Factor ss (TGF ss). Biological Chemistry, v. 401, n. 9, p. 1063-1069, AUG 2020. Web of Science Citations: 0.
FARIA, ALESSANDRA V. S.; CLERICI, STEFANO P.; DE SOUZA OLIVEIRA, PATRICIA F.; QUEIROZ, KARLA C. S.; PEPPELENBOSCH, MAIKEL P.; FERREIRA-HALDER, CARMEN V. LMWPTP modulates the antioxidant response and autophagy process in human chronic myeloid leukemia cells. Molecular and Cellular Biochemistry, v. 466, n. 1-2, p. 83-89, MAR 2020. Web of Science Citations: 0.
FARIA, ALESSANDRA V. S.; ANDRADE, SHEILA S.; REIJM, AGNES N.; SPAANDER, MANON C. W.; DE MAAT, MONIEK P. M.; PEPPELENBOSCH, MAIKEL P.; FERREIRA-HALDER, V, CARMEN; FUHLER, GWENNY M. Targeting Tyrosine Phosphatases by 3-Bromopyruvate Overcomes Hyperactivation of Platelets from Gastrointestinal Cancer Patients. JOURNAL OF CLINICAL MEDICINE, v. 8, n. 7 JUL 2019. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.