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November 1994

Growth Inhibition by Interferon Beta and Gamma of MDA 886Ln Monolayer Cells and Multicellular Tumor Spheroids: A Differentiation Therapy Model for Squamous Cell Carcinoma

Author Affiliations

From the Memorial Sloan-Kettering Cancer Center, New York, NY (Drs Sacks and Schantz); R-Klinika Felsozoldmali, Budapest, Hungary (Dr Racz); and the University of Texas M. D. Anderson Cancer Center, Houston (Dr Rosenblum).

Arch Otolaryngol Head Neck Surg. 1994;120(11):1267-1272. doi:10.1001/archotol.1994.01880350073013

Objective:  The ability of interferon beta (IFN-β) and interferon gamma (IFN-γ) to modulate growth and differentiation of squamous carcinoma was studied.

Design:  Two squamous carcinoma models (MDA 886Ln monolayer cells and multicellular tumor spheroids [MTSs], an in vitro system with three-dimensional in vivo—like structure) were used. Effects of interferons were examined with growth and differentiation assays.

Results:  In 5-day monolayer growth assays, both interferons (IFNs) exhibited dose-dependent growth inhibition between 0 and 104 U/mL; IFN-γ was more inhibitory than IFN-β (inhibitory concentration for 50% inhibition of 9 and 900 U/mL for IFN-γ and IFN-β, respectively). Multicellular tumor spheroid growth was examined by sizing MTSs over a 9-day growth period. Multicellular tumor spheroids were resistant to IFN-β with exposures of up to 50 000 U/mL. Similarly, MTSs were resistant to IFN-γ for the first several days, with growth inhibition becoming evident between days 7 to 9 of culture. As a marker of differentiation, transglutaminase activity was quantified after 5 days of treatment. Both IFNs induced increased transglutaminase activity in monolayer cells: IFN-β was twice as effective as IFN-γ. In contrast, 5-day treated MTSs showed no induction although their endogenous activity was higher. Flow cytometric analysis of monolayer cells for induction of class I and II major histocompatibility complex showed that both IFNs induced class I antigens but only IFN-γ could induce class II.

Conclusions:  With their three-dimensional architecture, MTSs were more resistant to IFN-induced growth inhibition and differentiation induction than monolayer cells. Thus, mode of growth (monolayer vs MTS) is an important factor in responsiveness to IFN treatment; this suggests that MTSs may produce information that is more relevant to in vivo usage than monolayer cells.(Arch Otolaryngol Head Neck Surg. 1994;120:1267-1272)

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