Platelet-dependent signaling and Low Molecular Weight Protein Tyrosine Phosphatase expression promote aggressive phenotypic changes in gastrointestinal cancer cells

Author(s)

Faria, Alessandra V. S. ^{[1, 2]} ; Yu, Bingting ^[1] ; Mommersteeg, Michiel ^[1] ; de Souza-Oliveira, Patricia F. ^[2] ; Andrade, Sheila S. ^[3] ; Spaander, Manon C. W. ^[1] ; de Maat, Moniek P. M. ^[4] ; Peppelenbosch, Maikel P. ^[1] ; Ferreira-Halder, V, Carmen ; Fuhler, Gwenny M. ^[1]

Affiliation

^[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

• Document type: Journal article
• Source: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE; v. 1868, n. 1 JAN 1 2022.
• Web of Science Citations: 0

Abstract

Over the last decades, some members of the protein tyrosine phosphatase family have emerged as cancer promoters. Among them, the Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP) has been described to be associated with colorectal cancer liver metastasis and poor prostate cancer prognosis. Of importance in the process of cancer progression and metastasis is the interaction between tumor cells and platelets, as the latter are thought to promote several tumor hallmarks. Here, we examine to what extent LMWPTP expression in tumor cells affects their interaction with platelets. We demonstrate that the gene encoding LMWPTP is overexpressed in upper gastrointestinal (GI) cancer cell as well as colorectal cancer, and subsequently employ cell line models to show that the level of this phosphatase may be further augmented in the presence of platelets. We demonstrate that tumor-platelet interaction promotes GI tumor cell proliferation. Additionally, using know-down/-out models we show that LMWPTP expression in cancer cells contributes to a more efficient interaction with platelets and drives platelet-induced proliferation. These data are the first to demonstrate that phosphatases play a positive role in the tumor-promoting activities of platelets, with LMWPTP emerging as a key player promoting oncogenic phenotypic changes in tumor cells. (AU)

• FAPESP's process: 17/26317-1 - InGrowth, biomimetic product developed by platelet bioactivation platform: applications in the veterinary and research and development areas
• Grantee: Sheila Siqueira Andrade
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• FAPESP's process: 18/00736-0 - MicroRNAs in stool and platelets biology from gastroenterology cancer patient samples that correlate with ACP1 protein tyrosine phosphatase: colorectal cancer screening
• Grantee: Alessandra Valéria de Sousa Faria
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 16/14459-3 - Human platelet lysate: from discard to value products in cell therapy and advanced cell-based medicine
• Grantee: Sheila Siqueira Andrade
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• FAPESP's process: 17/08119-8 - Hematogenous tumor metastasis in colon rectal cancer cells: influence of LMWPTP and 3-bromopyruvate
• Grantee: Alessandra Valéria de Sousa Faria
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/20412-7 - Low molecular weight protein tyrosine phosphatase in colorectal cancer: from the bench to product generation
• Grantee: Carmen Veríssima Ferreira
• Support Opportunities: Research Projects - Thematic Grants