抄録
The carcinoma cells in tissues break through the vessel wall into the blood stream and conversely pass through the vessel wall into distant tissues or organs. Thus, the cell-to-cell interaction between VSMCs and tumor cells is critical to the pathophysiological process of angiogenesis, vascular remodeling and metastasis. In this study, the growth rate of vascular smooth muscle cells (VSMCs), which were derived from aorta of mice deficient in the fibrinolytic factors; tissue-type plasminogen activator (t-PA−/-), urokinase (u-PA−/-), u-PA receptor (u-PAR−/-) and type 1 plasminogen activator inhibitor (PAI-1−/-), as well as wild-type (WT) mice, was investigated in the presence of mouse melanoma cells (B16). In the VSMCs cultured with a basal medium, there was no difference in the growth rate among the gene-lacking VSMCs and WT VSMCs. On the other hand, when these VSMCs were cultured with B16 cells in either the mixed culture or a double-chamber, only u-PAR−/-VSMCs showed a significantly lower growth rate. In addition, these suppressive effects on u-PAR−/-VSMCs were also observed in the presence of B16-derived conditioned medium (B16/CM). These effects on growth activity were partially associated with the levels of tyrosine phosphorylation of 77-kDa protein and mitogen-activated protein kinase (MAPK, p42/p44) activity. The findings suggest that u-PAR plays an important role in the proliferative response of VSMCs and that without u-PAR, there is no intracellular signaling for cell proliferation. [Jpn J Physiol 54 Suppl:S74 (2004)]
