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We determined the effect of cytokines on the proliferation and migration of cells isolated from the inner-third (white-white), middle-third (red-white), and outer-third (red-red) regions of bovine meniscus. Cells from the outer, or peripheral, region of the meniscus exhibited higher DNA synthesis in the presence of 10% serum compared with cells from the inner or central regions. Recombinant human platelet-derived growth factor-AB, hepatocyte growth factor/scatter factor, and bone morphogenic protein-2 stimulated DNA synthesis of all meniscal cells in a dose-dependent manner, with a two- to threefold maximal stimulation at 10 ng/ml. Cell migration was also stimulated by addition of cytokines. Platelet-derived growth factor and hepatocyte growth factor caused an increase in the migration of cells derived from all three zones, while interleukin-1 selectively stimulated the migration of outer-zone meniscal cells. Epidermal growth factor was much less effective and stimulated the migration of cells in the inner and outer zones by 40% to 50%, while bone morphogenic protein-2 and insulin-like growth factor-1 stimulated the migration of meniscal cells from the middle zone by 40% to 50%. The identification of cytokines that stimulate both the growth and migration of meniscal cells may provide new tools for modulation of meniscal healing.

Scatter factor (SF) is a glycoprotein which is secreted by mesenchymal cells and which causes cohesive epithelial cell colonies to spread out, separate into individual cells, and assume a fibroblastic morphology (i.e., to "scatter"). SF is now known to be identical or nearly identical to hepatocyte growth factor, a serum-derived mitogen for various normal cell types. SF, tumor necrosis factor-alpha (TNFa), and interleukin-1 (IL1) share the ability to stimulate scattering, motility, and protease production in a variety of human tumor cell types. SF and TNFa stimulate vascular endothelial cell motility in vitro and induce angiogenesis, the formation of new blood vessels, in vivo. These factors may participate in a cytokine network which regulates tumor invasion and metastasis directly by enhancing the malignant epithelial phenotype and indirectly by inducing tumor neovascularization.

We investigated the effects of human placental scatter factor (hSF), mouse scatter factor (mSF) and recombinant human hepatocyte growth factor (HGF) on motility and morphology of individual Madin-Darby canine kidney cells using a computerized cell tracking system. All three factors increased the velocity of individual cells and the ratio of moving to stationary cells. Similarly, all three factors caused changes in morphologic features of cells, leading to increased area, flatness, and polarity. Increases in area and flatness but not polarity were slightly greater with HGF than with hSF or mSF. These results suggest that SFs and HGF have similar effects on motility and morphology of isolated epithelial cells.

Scatter factor (SF) is a protein produced by fibroblasts, smooth muscle cells, and human placenta which scatter cohesive epithelial cell colonies and increases cellular motility. SF bound to concanavalin A and other lectins with high affinity. SF could also be stained with a glycoprotein specific stain. Incubation of producer cells (N-ras-transformed 3T3), with tunicamycin homolog A1 did not have any significant effect on the secretory activity of SF. The treatment of SF with N- and O-glycanases as well as endoglycosidase H had no effect on its activity. However, treatment of target (Madin Darby canine kidney) cells with tunicamycin A1, abolished the scattering response. These studies suggest that scatter factor is a glycoprotein, but glycosylation is not required for its secretion or activity by the producer cells; however, glycosylation of proteins in the target cells is required for SF action.

Scatter factor (SF) causes contiguous sheets of epithelium to spread and cells to separate from each other. SF also increases the velocity, area, and reduces the circularity of individual cells. These changes are mediated in part by alterations in protein synthesis, protein phosphorylation, cytoskeletal reorganization, and cell surface components. SF has been purified from the conditioned medium of ras transformed 3T3 cells and human placenta. Sequence information suggests that SF from 3T3 cells is closely related to hepatocyte growth factor. SF is a glycoprotein, but glycosylation is not necessary for its activity. Glycosylation of target cell proteins, however, is required for SF action.