Sacks P G, Racz T, Schantz S P, Rosenblum M G
Memorial Sloan-Kettering Cancer Center, New York, NY.
Arch Otolaryngol Head Neck Surg. 1994 Nov;120(11):1267-72. doi: 10.1001/archotol.1994.01880350073013.
The ability of interferon beta (IFN-beta) and interferon gamma (IFN-gamma) to modulate growth and differentiation of squamous carcinoma was studied.
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.
In 5-day monolayer growth assays, both interferons (IFNs) exhibited dose-dependent growth inhibition between 0 and 10(4) U/mL; IFN-gamma was more inhibitory than IFN-beta (inhibitory concentration for 50% inhibition of 9 and 900 U/mL for IFN-gamma and IFN-beta, respectively). Multicellular tumor spheroid growth was examined by sizing MTSs over a 9-day growth period. Multicellular tumor spheroids were resistant to IFN-beta with exposures of up to 50,000 U/mL. Similarly, MTSs were resistant to IFN-gamma 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-beta was twice as effective as IFN-gamma. 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-gamma could induce class II.
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.
研究β干扰素（IFN-β）和γ干扰素（IFN-γ）调节鳞状细胞癌生长和分化的能力。
使用两种鳞状细胞癌模型（MDA 886Ln单层细胞和多细胞肿瘤球体[MTS]，一种具有三维体内样结构的体外系统）。通过生长和分化试验检测干扰素的作用。
在为期5天的单层生长试验中，两种干扰素（IFN）在0至10⁴ U/mL之间均表现出剂量依赖性生长抑制；IFN-γ比IFN-β的抑制作用更强（IFN-γ和IFN-β的50%抑制浓度分别为9和900 U/mL）。通过在9天的生长周期内对MTS进行测量来检测多细胞肿瘤球体的生长。多细胞肿瘤球体对高达50,000 U/mL的IFN-β具有抗性。同样，MTS在培养的最初几天对IFN-γ也具有抗性，在培养的第7至9天生长抑制变得明显。作为分化标志物，在处理5天后对转谷氨酰胺酶活性进行定量。两种IFN均诱导单层细胞中转谷氨酰胺酶活性增加：IFN-β的效果是IFN-γ的两倍。相比之下，经5天处理的MTS尽管其内源活性较高，但未显示出诱导作用。对单层细胞进行流式细胞术分析以检测I类和II类主要组织相容性复合体的诱导情况，结果显示两种IFN均诱导I类抗原，但只有IFN-γ能诱导II类抗原。
由于其三维结构，MTS比单层细胞对IFN诱导的生长抑制和分化诱导更具抗性。因此，生长模式（单层与MTS）是对IFN治疗反应性的一个重要因素；这表明MTS可能产生比单层细胞更与体内应用相关的信息。
