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Published on: September 1, 2015
Cell type-specific control of human neuronectin secretion by polypeptide mediators and phorbol ester.
1Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Summary
Neuronectin (NEC1), an extracellular matrix protein, shows varied expression patterns. Its production is modulated by specific growth factors and signaling molecules, suggesting extrinsic control in different cell types and conditions like injury and tumors.
Area of Science:
- Cell Biology
- Developmental Biology
- Neuroscience
Background:
- Neuronectin (NEC1) is an extracellular matrix protein with a distinct rostrocaudal pattern in the adult central nervous system white matter.
- NEC1 is also found in smooth muscle, epithelial-mesenchymal junctions, and developing cartilage.
- Its expression is induced in dermal wounds, actinic keratoses, psoriatic lesions, and tumors.
Purpose of the Study:
- To investigate the regulatory mechanisms controlling Neuronectin (NEC1) secretion in various human cell types.
- To determine the role of specific growth factors and signaling molecules in NEC1 expression.
- To understand the extrinsic control of NEC1 in different cell lineages and pathological conditions.
Main Methods:
- Utilized cultured human neural and mesenchymal cells.
- Administered various regulatory polypeptides including fibroblast growth factors, tumor necrosis factor, platelet-derived growth factor, nerve growth factor, and transforming growth factor-beta (TGF-beta).
- Applied 12-O-tetradecanoyl phorbol-13-acetate (TPA) to assess modulation of NEC1 secretion.
Main Results:
- Several regulatory polypeptides significantly modulated NEC1 secretion in a cell-type-specific manner.
- Transforming growth factor-beta (TGF-beta) and 12-O-tetradecanoyl phorbol-13-acetate (TPA) exhibited both inducing and inhibitory effects on NEC1 secretion, dependent on the target cell.
- These modulatory effects were specific to NEC1 and not observed for other studied proteins.
Conclusions:
- NEC1 expression is under diverse extrinsic control mechanisms that vary across different cell lineages.
- Cellular production of NEC1 can be influenced by specific signaling pathways in response to tissue injury and neoplasia.
- These findings provide insights into the regulation of extracellular matrix protein expression in normal development and disease.
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