Couldwell W T, Yong V W, Dore-Duffy P, Freedman M S, Antel J P
Neuroimmunology Unit, Montreal Neurological Hospital and Institute, Canada.
J Neurol Sci. 1992 Jul;110(1-2):178-85. doi: 10.1016/0022-510x(92)90026-h.
Gliomas in vitro exhibit density-limited growth upon the attainment of confluency, an effect usually attributed to cell-cell contact inhibition. Since gliomas have been demonstrated to secrete an array of soluble factors which can enhance tumor growth, we undertook this study to ascertain whether production of soluble factors by the tumor may also inhibit growth in an autocrine manner, and whether production of such factors is associated with the growth phase of the glioma. We observed that cell-conditioned medium (supernatants) from non-confluent glioma cultures induced growth, while confluent culture supernatants produced pronounced growth suppression. These latter supernatants enhanced proliferation of non-transformed astrocytes. Supernatants derived from all stages of confluency produced inhibition of lymphocyte proliferation. To characterize these factors, dialyzed supernatant was tested and found to continue to produce lymphocyte suppression but no glioma growth limitation. Growth of tumors in indomethacin or in acetylsalicylic acid to abolish prostanoid synthesis abrogated the inhibitory influence on glioma growth but only partially reversed the lymphocyte suppressive capacity. These studies suggest that gliomas do produce a growth phase dependent autocrine inhibitory factor(s), and that the production of these small molecular weight factors is at least partially under control of the cyclooxygenase pathway.
体外培养的神经胶质瘤在达到汇合状态时表现出密度限制生长，这种效应通常归因于细胞间接触抑制。由于已证明神经胶质瘤会分泌一系列可促进肿瘤生长的可溶性因子，我们开展了这项研究，以确定肿瘤产生的可溶性因子是否也可能以自分泌方式抑制生长，以及这些因子的产生是否与神经胶质瘤的生长阶段相关。我们观察到，来自未汇合神经胶质瘤培养物的细胞条件培养基（上清液）可诱导生长，而汇合培养物的上清液则产生明显的生长抑制作用。后一种上清液可增强未转化星形胶质细胞的增殖。来自所有汇合阶段的上清液均能抑制淋巴细胞增殖。为了表征这些因子，对透析后的上清液进行了测试，发现其继续产生淋巴细胞抑制作用，但没有神经胶质瘤生长限制作用。在吲哚美辛或乙酰水杨酸中培养肿瘤以消除前列腺素合成，可消除对神经胶质瘤生长的抑制作用，但只能部分逆转淋巴细胞抑制能力。这些研究表明，神经胶质瘤确实会产生一种生长阶段依赖性自分泌抑制因子，并且这些小分子因子的产生至少部分受环氧合酶途径的控制。
