Inhibition of Metastatic Cancer in Mice via Atopaxar: A Research Protocol

Abstract

Introduction: When cancer becomes metastatic, tumour cells intravasate out of the primary tumour and spread to other organs, causing about 90% of cancer deaths. One way circulating tumour cells (CTCs) metastasize is by interacting with platelets, resulting in tumour cell-induced platelet aggregation (TCIPA) that shields CTCs from immune attack. Previous studies suggest that tumour cells promote metastasis and induce TCIPA by activating protease-activated receptor-1 (PAR-1) on platelets. Therefore, this study aims to investigate whether administering Atopaxar, a PAR-1 antagonist that has not yet been studied in cancer as other PAR-1 antagonists have, can limit metastasis in mouse models.

Methods: We will assess the effectiveness of Atopaxar and a placebo (or control) on adult C57BL mice inoculated with GFP-transfected Lewis lung carcinoma cells. Flow cytometry of blood samples taken 7, 14, and 21-days post-inoculation will be performed to quantify the number of GFP+ cells and activated CD8+ (cytotoxic) T cells in the samples.

Results: We expect that the Atopaxar treated mice will have reduced numbers of CTCs and higher numbers of cytotoxic T cells, suggesting that the inhibition of TCIPA via Atopaxar will correlate with reduced shielding of CTCs and metastasis rates.

Discussion: These results could provide novel insight into the use of PAR-1 antagonists in confining cancer to its primary site in patients and inhibiting CTCs’ function as a seed for metastases.

Conclusion: Since CTCs will usually be present in the blood even after removal of a secondary tumour, limiting metastasis can significantly improve the prognosis and wellbeing of patients.