Abstract
The various fibroproliferative disorders affecting humans have in common excess fibroblast activity and persistent overexpression or dysregulated activity of transforming growth factor beta (TGF-β). Cancer has many similar characteristics. Antineoplastic drugs can downregulate fibroblast activity and cytokine growth factors. This study evaluates the effect of six antineoplastic drugs on keloid and Dupuytren’s disease fibroblasts. Keloid, normal scar, Dupuytren’s affected palmar fascia, and normal palmar fascia fibroblasts were grown and seeded into Fibroblast Populated Collagen Lattices (FPCLs). The FPCLs were treated with one of six antineoplastic drugs or left untreated as controls. At 7 days, supernatants were extracted from all FPCLs and assayed for expression of Transforming Growth Factor beta (TGF)-β1 and TGF-β2. All six antineoplastic drugs significantly inhibited FPCL contraction in both fibroproliferative conditions compared with the untreated controls (p β1 and TGF-β2 expression was downregulated in the supernatants of all FPCLs by the drug exposure. Cytotoxicity did not occur in these studies and was not the reason for the results. Although antineoplastic drugs can have significant side effects when given systemically, these results may be minimized when given to small areas involved in fibroproliferative scarring or when given topically or intralesionally. These in vitro results suggest that antineoplastic drugs may have a utility for treating various fibroproliferative disorders and warrant further investigation.
Highlights
Various fibroproliferative disorders appear to have similar pathophysiologic features
Keloid fibroblasts caused a significantly greater contraction of the Fibroblast-Populated Collagen Lattices (FPCLs) at each measuring point compared with normal scar fibroblasts (p < 0.01) (Figure 1(a))
Fibroblasts from Dupuytren’s affected palmar fascia caused a significantly greater degree of contraction of the FPCL compared with the normal control palmar fascia beginning on day 3 (p < 0.05) (Figure 1(b))
Summary
Various fibroproliferative disorders appear to have similar pathophysiologic features These disorders such as hypertrophic scar, keloid, rhinophyma, periprosthetic breast capsules, and Dupuytren’s contracture have in common active fibroblast activity and overexpression or increased reactivity to the fibrogenic isoforms of Transforming Growth Factor beta (TGF-β) [1]-[8]. Agents that tend to downregulate fibroblast activity and/or downregulate, abrogate, or neutralize the fibrogenic isoforms of TGF-β (TGF-β1 and TGF-β2) have been suggested to treat some or all of the fibroproliferative disorders discussed These agents include neutralizing antibodies to TGF-β1 and TGF-β2, the non-fibrotic isoform TGF-β3, interferon gamma, Interferon alpha-2b, mannose-6-phosphate, the decorins, imiquimod, and N-AcetyloL-Cysteine (NAC) [1] [2]. All of these have shown some degree of success in in vitro or animal models
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