Increased thrombin levels within the lungs of breast cancer patients correlates with PAR1 overexpression on the primary tumor and pulmonary metastasis development Free

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Thrombin´s receptor PAR1 is involved in the invasion process of breast cancer. It is present on breast cancer cell lines, and mediates its angiogenic, and proliferative responses. Furthermore its expression levels correlated with degree of invasiveness. The aim of this study was to identify PAR1 potential as mediator of tumor cell chemotaxis preferentially to the lungs of patients with metastatic breast cancer. In a cohort of 50 patients with ductal carcinoma, we assessed PAR1 expression on the primary tumor and thrombin leves in their bronchoalveolar lavage fluids. Chi-square and log rank test were used to determine differences between proportions of PAR1 expression, thrombin levels and the development of metastases, mortality and survival distributions respectively. P values ≤ 0.05 were considered significant. The median follow-up was 88 months (2-120 months). We found 29/50 patients (58%) overexpressed PAR1; 26/50 patients (52%) shown high levels of thrombin in their lungs (3.5X10^-9M; 2.5x10^-9M - 7.9X10^-9M); all of them were overexpressing PAR1 (P<0.0001). Only 12/50 patients (24%) developed metastases to the lung. All of them were positive for PAR1 and thrombin.This relationship was highly significant (P= 0.0005 and P=0.0002 respectively) when compared with the rest of the group. We also found a statistically significant correlation between patients showing PAR1 and thrombin leves in lungs and higher mortality (P<0.0001 and P=0.0001). Our data is suggesting PAR1 found in breast cancer patients may be a key mediator in the tumor cell chemotaxis to the find its ligand thrombin, present within the lungs and metastasize.

This work was supported by CONACyT (Salud-2003-C01-3)