Abstract Number: OC 58.1
Meeting: ISTH 2021 Congress
Background: Phosphorylation is the most common post-translation modification and regulatory mechanism of proteins. For many enzymes, phosphorylation leads to a reversible and fast modulation of enzymatic activity. The Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP) has been associated with metastasis in Colorectal Cancer (CRC), as it was observed higher expression of this enzyme in both primary and secondary tumor sites (liver). Along the metastasis process, the tumor cells’ interaction with blood components is crucial to their survival at circulation. The investigation of the molecular signaling events in cancer cells contributing to platelet-mediated oncogenic stimulation might a strategy to overcome metastasis. Based on that, we focus on the molecular crosstalk triggered by CRC cell-platelets interaction, especially regarding the role of LMWPTP in this process.
Aims: Elucidate the role of LMWPTP in both platelets and CRC to support CRC’s aggressive phenotype.
Methods: Expression analysis (RNA and protein) from platelets and biopsies from CRC patients (Ethical-Committee: NL66029.078.18), public repositories; migration assay (2D and 3D culture); colony formation derived from CRC cell lines; validation of the biological relevance of phosphatase by using LMWPTP knocked out by CRISPR/Cas9 in a CRC cell line.
Results: Tumor and platelets play reciprocal actions in the pre-metastatic niche regarding LMWPTP, which appears to be upregulated in both tumor cells and platelets in cancer, with these cell types further reciprocally increasing LMWPTP expression. Patients suffering from CRC have a higher LMWPTP expression in platelets, which was directly associated with platelet hyperactivity, as well as, LMWPTP is overexpressed in CRC, which supports stronger interaction with platelets promoting proliferation and leading to increase the LMWPTP expression in tumor cells, potentially initiating a positive feedback loop.
Conclusions: In summary, LMWPTP emerged as a potential key-player to reprogram platelet and cancer cells on tumor microenvironment, promoting advantages for tumor aggressive phenotype, and supporting tumor cell-induced platelet activation (Figure 1).
|São Paulo Research Foundation grants 2017/08119-8 and 2018/00736-0
|São Paulo Research Foundation grant 2015/204127
To cite this abstract in AMA style:Faria AVS, Yu B, Andrade SS, Peppelenbosch M, Fuhler G, Ferreira-Halder CV. The “Double-edged Sword”: The Role of LMWPTP in Platelet Hyperactivity in Cancer Patients [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/the-double-edged-sword-the-role-of-lmwptp-in-platelet-hyperactivity-in-cancer-patients/. Accessed February 25, 2024.
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