{'fraction_non_alphanumeric': 0.034432234432234435, 'fraction_numerical': 0.017582417582417582, 'mean_word_length': 5.04424778761062, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
The Effect of Activated Protein C on Prostate Tumor Cell Invasion

We investigated the role of the prostate tumor cell associated protein, thrombomodulin (TM), in prostate tumor cell invasion in vitro. Specifically, we determined if TM, thrombin, protein C, and activated protein C (APC) affect invasion by regulating interactions between plasminogen activator inhibitor I (PAI‐1) and urokinase type plasminogen activator (uPA). We first determined that monoclonal antibodies to the extracellular chondroiten sulphate domain of TM increased the ability of DU‐145 cell lines to migrate in a modified Boyden chamber. Addition of thrombin and protein C did not affect DU‐145 invasion. Addition of 0–10 ng/ml APC also did not affect tumor cell invasion, however, higher than 10 ng/ml slightly decreased DU‐145 invasion. Since APC has been shown to affect tumor cell invasion in ovarian cancer by competing with uPA for PAI‐1, we further determined if APC also regulates tumor cell invasion in prostate cancer by competing for PAI‐1. In the presence of uPA and PAI‐1, APC competed with uPA for binding to PAI‐1, enabling uPA to increase the invasiveness of DU‐145 cells. We conclude that in the presence of TM, thrombin, protein C, PAI‐1 and uPA, TM regulates tumor cell invasion by generating APC, which can bind to PAI‐1, freeing uPA to facilitate tumor cell invasion.