Growth inhibition by interferon beta and gamma of MDA 886Ln monolayer cells and multicellular tumor spheroids: A differentiation therapy model for squamous cell carcinoma Journal Article
| Authors: | Sacks, P. G.; Racz, T.; Schantz, S. P.; Rosenblum, M. G. |
| Article Title: | Growth inhibition by interferon beta and gamma of MDA 886Ln monolayer cells and multicellular tumor spheroids: A differentiation therapy model for squamous cell carcinoma |
| Abstract: | 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. © 1994, American Medical Association. All rights reserved. |
| Keywords: | controlled study; human cell; squamous cell carcinoma; carcinoma, squamous cell; laryngeal neoplasms; cancer growth; dose response; flow cytometry; lymphatic metastasis; cell differentiation; tumor cells, cultured; enzyme activity; cancer resistance; recombinant gamma interferon; major histocompatibility antigen class 2; major histocompatibility complex; beta interferon; drug formulation; major histocompatibility antigen class 1; interferon-beta; minimum inhibitory concentration; multicellular spheroid; interferon type ii; monolayer culture; tumor spheroid; human; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; protein glutamine gamma glutamyltransferase; transglutaminases |
| Journal Title: | Archives of Otolaryngology - Head & Neck Surgery |
| Volume: | 120 |
| Issue: | 11 |
| ISSN: | 0886-4470 |
| Publisher: | American Medical Association |
| Date Published: | 1994-11-01 |
| Start Page: | 1267 |
| End Page: | 1272 |
| Language: | English |
| DOI: | 10.1001/archotol.1994.01880350073013 |
| PROVIDER: | scopus |
| PUBMED: | 7917212 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
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