MODULATION OF THE ANCHORAGE-INDEPENDENT PHENOTYPE OF HUMAN LUNG FIBROBLASTS OBTAINED FROM FIBROTIC TISSUE FOLLOWING CULTURE WITH RETINOID AND CORTICOSTEROID

Fibroblast heterogeneity has been documented in fibrotic tissue from l ung and skin. differences have been demonstrated in proliferative rate s in fibroblasts derived from fibrotic lung tissue as compared to norm al. Fibroblast lines derived from adult fibrotic lung tissue and neona tal normal lung tissue exhibit colony growth in soft agarose culture, whereas fibroblast cell lines from normal adult lung tissue do not. Th e characteristic of anchorage-independent growth is consistent with th e aggressive nature of the disease and with developmental lung growth. In this study, fibrotic lung fibroblasts were exposed to growth diffe rentiating factors to determine whether the anchorage-independent phen otype can be modulated. The results indicate that treatment of fibroti c lung fibroblasts with retinoic acid, known to modify matrix gene exp ression and induce differentiation, inhibits the cells ability ro form colonies under soft agarose growth. Treatment with all-trans-retinoic acid yielded the greatest effect inhibiting both IPF and neonatal lun g fibroblast anchorage-independent growth approximately 90% at 10(-6) M. Treatment of IPF fibroblasts with all-trans-retinoic acid also inhi bited corticosteroid-induced colony growth. Modulation of the ''fibrot ic'' fibroblast phenotype through retinoid therapy may prove beneficia l as a potential therapeutic strategy.