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Fig. 1. Colon-cancer-cell-derived TGF-ß is necessary and sufficient to stimulate invasion of myofibroblasts into collagen type I and Matrigel. (A) Myofibroblast spheroids were embedded in a collagen type I gel on top of which serum-free DMEM was added without (untreated), with 10⁶ HCT-8/E11 cells or with CM^HCT-8/E11 cells, in the presence of control IgG1 or of neutralizing TGF-ß mAb. (B) Myofibroblast spheroids in collagen type I were cultured for 7 days with the indicated treatments. The medium was refreshed on days 3 and 5. A representative phase-contrast micrograph is shown for each condition, taken after 48 hours (panel A) or after 7 days (panel B). Experiments in A and B were repeated at least three times and had similar results. Scale bars, 100 µm. (C) Single-cell myofibroblasts at a density of 4x10⁵ were seeded upon a Matrigel coated filter. HCT-8/E11 cells at a density of10⁶ were seeded or rTGF-ß1 was placed in the lower compartment in the presence of control IgG1 or neutralizing TGF-ß mAb. Bars indicate means of three results ± s.d. Asterisks show statistically significant difference from untreated control.

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