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: