In addition to providing a structural support, the extracellular matrix (ECM) exerts important influences on cellular proliferation, migration and differentiation, and affects such processes as embryogenesis, wound healing, regeneration and angiogenesis. A convenient preparation is the gel extract of the EHS tumor, which is biochemically and structurally similar to an endothelial type of basement membrane. This gel promotes differentiation in endothelial cells, hepatocytes, Sertoli cells and Schwann cells. We examined its effect on smooth muscle cells because of the problem that tbese cells de-differentiate in culture and lose their contractile properties. We found that subconfluent rat aortic smooth muscle cells proliferated faster on the EHS gel. Their growth was also less inhibited when serum was withdrawn than was the case for cells on plastic alone. This suggasted that ECM components might be storing growth factors produced by the cells or found in serum. The individual matrix components, laminin, or heparin were unable to reproduce the effects of the gel. Electron microscopy indicated that cells grown in EHS gel produced less of their own ECM. Also, the cells grown in the gel were grouped in small bundles. Basement membrane components may thus promote growth by enhancing cell to cell contact and subsequent paracrine functions. However, when confluent quiescent cells were refed, the EHS gel inhibited growth. (Heparin, but not laminin, also inhibited growth). However, the electron microscopic appearance remained that of a non-contractile cell, and there was no increase in intracellular calcium in response to depolarization by potassium chloride. For this reason we will not be pursuing this project further, but it is clear that basement membrane components influence smooth muscle cell growth in vitro, and in vivo, may influence such properties as atherosclerosis, embryogenesis and the response to arterial wounds, such as those produced by angioplasty.
