Steller M A, Mok S C, Yeh J, Fulop V, Anderson D J, Berkowitz R S
Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
J Reprod Med. 1994 Mar;39(3):209-16.
Trophoblastic cells abundantly express epidermal growth factor (EGF) receptors, which, when activated by EGF or transforming growth factor-alpha, can influence cellular growth and metabolism. Various lymphocyte and macrophage cytokines have been found to influence the proliferation of human choriocarcinoma (CCA) cells in vitro. In the current study we investigated the possibility that certain cytokine effects are mediated by changes in EGF receptor expression. JEG-3 human CCA cells were incubated with varying concentrations of interleukin 1-alpha (IL-1 alpha), interleukin 1-beta (IL-1 beta), interleukin 2, gamma-interferon, granulocyte-macrophage colony stimulating factor and tumor necrosis factor-alpha (TNF), and the expression of EGF receptor was measured by radioimmunoassay using a murine monoclonal antibody with specificity for the EGF receptor. Proliferative or growth suppressive effects of the cytokines were assessed by quantitative analysis of the DNA in the cell culture wells. Macrophage-derived cytokines IL-1 alpha, IL-1 beta and TNF significantly suppressed cell growth; this was associated with a significant increase in EGF receptor expression. The other cytokines had no significant effect on either EGF receptor expression or cell growth. We also studied the expression of EGF mRNA in JEG-3, Jar and BeWo CCA cell lines. By reverse transcription followed by polymerase chain reaction, low levels of EGF mRNA were detected in all three cell lines. Therefore, EGF may be synthesized by JEG-3, Jar and BeWo CCA cell lines to participate in an autocrine growth pathway. Our findings support the concept that cytokines may act as paracrine mediators of autocrine processes involved in CCA cell growth regulation by modulating growth factor receptor expression.
滋养层细胞大量表达表皮生长因子（EGF）受体，当该受体被EGF或转化生长因子-α激活时，可影响细胞的生长和代谢。已发现多种淋巴细胞和巨噬细胞细胞因子在体外可影响人绒毛膜癌（CCA）细胞的增殖。在本研究中，我们探讨了某些细胞因子的作用是否是由EGF受体表达的变化介导的。将JEG-3人CCA细胞与不同浓度的白细胞介素1-α（IL-1α）、白细胞介素1-β（IL-1β）、白细胞介素2、γ-干扰素、粒细胞-巨噬细胞集落刺激因子和肿瘤坏死因子-α（TNF）一起孵育，使用对EGF受体具有特异性的鼠单克隆抗体通过放射免疫测定法测量EGF受体的表达。通过对细胞培养孔中DNA的定量分析评估细胞因子的增殖或生长抑制作用。巨噬细胞衍生的细胞因子IL-1α、IL-1β和TNF显著抑制细胞生长；这与EGF受体表达的显著增加有关。其他细胞因子对EGF受体表达或细胞生长均无显著影响。我们还研究了JEG-3、Jar和BeWo CCA细胞系中EGF mRNA的表达。通过逆转录随后进行聚合酶链反应，在所有三个细胞系中均检测到低水平的EGF mRNA。因此，EGF可能由JEG-3、Jar和BeWo CCA细胞系合成，以参与自分泌生长途径。我们的研究结果支持这样一种概念，即细胞因子可能通过调节生长因子受体表达，作为参与CCA细胞生长调节的自分泌过程的旁分泌介质。
