Evidence that thrombin present in lungs of patients with pulmonary metastasis may contribute to the development of the disease

Early cellular events in the lung which may lead to the development of pulm onary metastases (PM) are still poorly understood. Thrombin, a key componen t of the coagulation cascade, may be involved in the development of PM as i t has been shown to be an enhancer of platelet-tumor interaction in vitro a nd metastasis in vivo, and because it has been found in high levels in lung s from patients with PM. In this study, we assessed the potential role of t hrombin in promoting PM by inducing an enhancement of tumor cell adhesion t o platelets and tumor cell chemoinvasion and proliferation. We used broncho alveolar lavage fluid (BALF) from 20 patients with PM. Results were compare d with those from healthy controls. We found an enhancement of adhesion of PM-BALF-treated tumor cells to untreated platelets. BALF from patients with PM significantly increased chemoinvasion and proliferation in three human tumor cell lines. These activities were attenuated significantly by a throm bin inhibitor: hirudin. These results indicate that the thrombin present in the lungs of patients with PM is, at least in part, responsible for their adhesive, invasive and mitogenic activity on three different tumor cell lin es. They also suggest that thrombin may be involved in the development of P M. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.