Sarcoma-like cells (SCLs) were derived from endarterectomized tissue of a single chronic thromboembolic
pulmonary hypertension (CTEPH) patient during incubation of those thrombi at second passage as described at our previous report. These cells had malignant potential, with an increased expression of matrix metalloproteinase-14 (MMP-14), leading to
tumor emboli within pulmonary arteries in in vivo studies. The purpose of this study was to perform a more detailed evaluation of the characteristics of SCLs, and to elucidate the role of the increased expression of MMP-14 expression in the growth and death of these cells. In order to elucidate the characteristics of SCLs and to confirm the
protein expression of MMP-14, three-dimentional culture, invasion assays, a Western blot analysis and immunohistochemical studies were performed. To examine the role of MMP-14 in
tumorigenesis, the
metalloproteinase inhibitor,
batimastat, was administered to SCID mice which were subcutaneously injected with SCLs. Those mice were sacrificed on day 14 and the
tumor volume was evaluated. A Western blot analysis showed the increased expression of MMP-14 in comparison to the expression in
lung adenocarcinoma cells (A549). Immunohistochemistry showed that SCLs were positive for
vimentin, MMP-14, MMP-2 and CD44. However, endothelial markers, such as CD31 and
von Willebrand factor (vWF), were negative. The in vivo studies demonstrated that
batimastat could suppress the growth of the subcutaneous
tumors formed by the SCLs. This study suggested that
MMPs had critical roles on the pathological activities of SCLs and that
batimastat might have anti-proliferative and anti-invasive effects on these cells.