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Low molecular weight protein tyrosine phosphatase in colorectal cancer: from the bench to product generation

Grant number: 15/20412-7
Support type:Research Projects - Thematic Grants
Duration: July 01, 2016 - June 30, 2020
Field of knowledge:Biological Sciences - Biochemistry - Enzymology
Principal Investigator:Carmen Veríssima Ferreira
Grantee:Carmen Veríssima Ferreira
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Assoc. researchers:Daniel Martins-de-Souza ; Ruy Carlos Ruver Beck ; Sheila Siqueira Andrade
Associated scholarship(s):18/03593-6 - Tumor-educated platelets and metastasis: relevance of LMWPTP and extracellular vesicles in Colorectal Cancer, BP.DR
17/08119-8 - Hematogenous tumor metastasis in colon rectal cancer cells: influence of LMWPTP and 3-bromopyruvate, BP.DR

Abstract

Over the past decade, the groups led by Prof. Carmen Veríssima Ferreira and Prof. Maikel Peppelenbosch have explored signal transduction pathways in order to define the action mechanisms of antitumor candidates and for identifyng molecular targets related with the aggressiveness and resistance of tumor cells. In this context, we have investigated cell lines and biopsies of patients with prostate and colorectal tumors and identified the low molecular weight protein tyrosine phosphatase (LMWPTP) as one of indicators of aggressiveness/metastasis. CRC was choosen as model because we have stablished a set of CRC cell lines with low and high level of the LMWPTP expression. Besides, currently we are taking part in a Dutch National Programme for CRC screening, therefore, we have been built up a collection of stool samples (microRNAs). Therefore, the thematic project will address four main questions: 1) Could the high expression/activity of LMWPTP in colorectal cancer (CRC) cells control the exosomes biogenesis and composition (proteins and microRNAs)? 2) Could the high expression/activity of LMWPTP in colorectal cancer (CRC) cells influence their interaction with platelets (first stage of the hematogenous dissemination of the tumor)? If so, it could explain at least in part, the pro-metastasis action of this phosphatase; 3) Could this enzyme and/or microRNAs modulated by this enzyme be used as biomarkers (from liquid biopsy - stool samples) for diagnosis, prognosis and treatment monitoring?; 4) Could the pharmaceutical formulation containing the 3-bromopyruvate, effectively inhibiting the intracellular LMWPTP, decreasing the tumor cells-platelets aggregates and affecting the release of exosomes containing pro-metastatic factors? Therefore, we point out as the main contributions of the thematic project: a) the identification of new biomarkers that can be detected without the need of biopsy - the most widely used methods for early diagnosis of CRC are faecal occult blood testing and colonoscopy. Although these tests have improved survival rates across the CRC, the occult blood testing has low sensitivity and colonoscopy is expensive and invasive. In addition, certain foods and medications can lead to false-positive results of the occult blood test. Therefore, innovation in cheaper biomarkers and methods less invasive and more precise become highly relevant; b) the use of the LMWPTP as a target for inhibiting the first stage of hematogenous dissemination - the efficiency of the spread of tumor cells depends, in part, on their capacity to form mixed aggregates with blood cells, primarily platelets; c) the development of pharmaceutical formulation containing 3-bromopyruvate (3BP) encapsulated in exosomes derived from normal colon cells - despite the great potential of 3BP as antitumoral, it has failed in the clinical trials due to its toxic effect in erythrocytes. Therefore, pharmaceutical formulations that reduce or prevent this side effect are highly desirable. Finally, since this proposal is a technological cooperation between researchers from The Netherlands (Erasmus University of Rotterdam) and Brazil (Unicamp, Unifesp and UFRGS), we foreseen actions to add impact of the proposal for all institutions involved: to organize two meetings for following up the progress of the project; to provide training for the members of involved groups and to find new partners to increase the number and diversity of patient samples. (AU)

Matéria(s) publicada(s) na Agência FAPESP sobre o auxílio:
Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment 
Articles published in other media outlets (30 total):
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UOL: Enzima abundante em células tumorais poderá monitorar tratamento do câncer (11/Nov/2020)
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)
Sound Health and Lasting Wealth (Nigéria): 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)
Your Mag: Researchers investigate protein phosphatase to identify new treatments for cancer, other diseases (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)
Sciencenewsnet.in: 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: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
The Uncover Reality: 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)
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, CARMEN V.; FUHLER, GWENNY M. Platelets in aging and cancer-{''}double-edged sword{''}. CANCER AND METASTASIS REVIEWS, 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.
FERREIRA-HALDER, CARMEN VERISSIMA; DE SOUSA FARIA, ALESSANDRA VALERIA; ANDRADE, SHEILA SIQUEIRA. Action and function of Faecalibacterium prausnitzii in health and disease. BEST PRACTICE & RESEARCH IN CLINICAL GASTROENTEROLOGY, v. 31, n. 6, p. 643-648, DEC 2017. Web of Science Citations: 21.

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