Abstract
Neuronectin (NEC1) is a human extracellular matrix (ECM) protein expressed with a unique rostrocaudal pattern in white matter of the normal adult central nervous system. In addition, NEC1 is expressed in normal fetal and adult smooth muscle, along certain epithelial-mesenchymal junctions, and transiently in developing fetal cartilage. Region-specific induction of NEC1 is found in dermal wounds and in the reactive stroma of actinic keratoses, psoriatic skin lesions, and a range of malignant tumors. One explanation for these diverse tissue patterns is that cells capable of producing NEC1 are widely distributed in neural and mesenchymal tissues, but they become NEC1 producers only when induced by region-specific differentiation signals. In this study, we used cultured human cells to show that several regulatory polypeptides, including fibroblast growth factors, tumor necrosis factor, platelet-derived growth factor, nerve growth factor, and transforming growth factor-beta (TGF-beta), as well as 12-O-tetradecanoyl phorbol-13-acetate (TPA), modulate NEC1 secretion, with distinct patterns of inducing and inhibitory activities in different neural and mesenchymal cell types. TPA and TGF-beta act both as inducers and inhibitors of NEC1 secretion, depending on the target cell. These effects are specific for NEC1 and are not seen for several other secreted and membrane proteins studied. We suggest that NEC1 expression comes under different modes of extrinsic control in different cell lineages and in response to tissue injury and neoplasia.