Growth inhibition of vascular smooth muscle cells derived from urokinase receptor (u-PAR)-deficient mice in the presence of carcinoma cells.
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 supplemented with 10% fetal calf serum (FCS), there was no difference in the growth rate among the gene-lacking VSMCs and WT VSMCs, indicating that these fibrinolytic factors were not involved in the FCS-mediated cell proliferation. 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). The growth rate of all the VSMCs except u-PAR(-/-) VSMCs was increased in the presence of B16/CM. The degree of the increase in cell number was comparable to that obtained with FCS. These effects on growth activity were partially associated with the levels of 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.
Ueshima
Shigeru
S
Department of Physiology, Kinki University School of Medicine, 377-2 Ohnohigashi, Osakasayama City, 589-8511 Osaka, Japan.
Fukao
Hideharu
H
Okada
Kiyotaka
K
Matsuo
Osamu
O
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D003470:Culture Media / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*; D017395:Plasminogen Activator Inhibitor 1 / Q000172:deficiency / Q000502:physiology; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D010959:Tissue Plasminogen Activator / Q000172:deficiency / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000172:deficiency / Q000502:physiology
D003470:Culture Media; D017077:Culture Media, Conditioned; D017395:Plasminogen Activator Inhibitor 1; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D020928:Mitogen-Activated Protein Kinases; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator