DENSITY-DEPENDENT AND PROLIFERATION-STATUS-DEPENDENT EXPRESSION OF T-CADHERIN, A NOVEL LIPOPROTEIN-BINDING GLYCOPROTEIN - A FUNCTION IN NEGATIVE REGULATION OF SMOOTH-MUSCLE CELL-GROWTH

The atypical low density lipoprotein (LDL) binding proteins (M-r 105 a nd 130 kDa; p105 and p130) in human aortic medial membranes and cultur ed human and rat aortic smooth muscle cells (SMC) have recently been i dentified as the cell adhesion glycoprotein T-cadherin, Although cadhe rins are generally recognized to be important regulators of morphogene sis, the function of T-cadherin in the vasculature is poorly understoo d. This study has examined the relationship between expression of T-ca dherin and the density and proliferation status of SMC, T-cadherin (p1 05 and p130) levels in SMC lysates mere measured on Western blots usin g ligand-binding techniques. T-cadherin expression was dependent upon cell density, and maximal levels mere achieved at confluency. T-cadher in levels mere reversibly modulated by switching cultures between seru m-free (upmodulation) and serum-containing (downmodulation) conditions . Platelet-derived growth factor (PDGF)-BB, epidermal growth factor (E GF) or insulin-like growth factor (IGF) elicited a dose- and time-depe ndent downmodulation that was reversible after transfer of SMC to grow th factor-free medium. Our results support the hypothesis that T-cadhe rin may function as a negative determinant of cell growth, (C) 1998 Fe deration of European Biochemical Societies.