Dynamics of differentiation in human epidermoid squamous carcinoma cells (A431) with continuous, long-term gamma-IFN treatment.
We investigated the long-term effects of continuous gamma interferon (gamma-IFN) treatment on A431, a human squamous carcinoma cell line. Cells were grown in an in vitro culture system, which over time produces cohesive cell masses ("tumoroids") exhibiting three-dimensional, histotypically differentiated structures, e.g., keratin "pearls", intercellular bridges (desmosomes), elongated flattened cells (squames) and stratification. The effects of gamma-IFN on cell growth, morphology and stage of differentiation were assessed at different treatment times by light and electron microscopy and by immunohistochemical staining using antibodies to keratins 1 and 14 and to filaggrin, markers of specific stages of keratinocyte differentiation. Our results show that A431 cells have the capacity for spontaneous differentiation, that this capacity is significantly enhanced and accelerated by gamma-IFN treatment leading to terminal differentiation and extensive cell death by 2 wk. Despite continuous exposure to IFN, a small number of viable, undifferentiated cells remain. Their proliferation, evident by 3 wk, reconstitutes the tumoroid which once again contains the full range of differentiating cell types.
Ridge
J
J
Center for Biologics Evaluation and Research, FDA, Bethesda, Maryland 20892.
Muller
J
J
Noguchi
P
P
Chang
E H
EH
D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D000091344:Filaggrin Proteins; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology*; D007382:Intermediate Filaments / Q000648:ultrastructure; D007633:Keratins / Q000032:analysis; D008854:Microscopy, Electron; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007633:Keratins; D007371:Interferon-gamma