Stiles J D, Ostrow P T, Balos L L, Greenberg S J, Plunkett R, Grand W, Heffner R R
Department of Pathology, Buffalo General Hospital, NY 14263, USA.
J Neuropathol Exp Neurol. 1997 Apr;56(4):435-9. doi: 10.1097/00005072-199704000-00012.
Because the prominent neovascularization characteristic of high grade primary brain tumors is composed mostly of vascular smooth muscle cells (VSMC), we studied the expression of the potent smooth muscle mitogen endothelin-1 (ET-1) and one of its secretagogues, transforming growth factor beta 1 (TGF-beta 1) in a series of astrocytic tumors. TGF-beta 1 is also of interest due to its known activity as an angiogenic factor. Using immunohistochemical methods, we examined 30 surgical cases: 10 glioblastoma multiforme, 10 anaplastic astrocytomas, and 10 low-grade astrocytomas. Using a monoclonal antibody to TGF-beta 1 and a polyclonal antibody to ET-1, we detected both growth factors in all cases of glioblastoma examined. In cases of anaplastic astrocytoma, 4 tumors were positive for both factors; 2 contained only ET-1; 2 contained only TGF-beta 1; and 2 exhibited no tumor cell immunoreactivity for either factor. In low-grade astrocytoma, 4 of 10 tumors showed weak ET-1 immunoreactivity; 2 of those contained TGF-beta 1 immunopositive tumor astrocytes: 6 tumors were negative for both factors. In all tumors that expressed both factors, serial sections showed that regions of ET-1 immunopositivity also tended to be positive for TGF-beta 1. Endothelial cells within all tumors were positive for ET-1. ET-1 and TGF-beta 1 are present in human astrocytomas and their expression correlates with tumor vascularity and malignancy. These results suggest roles for both ET-1 and TGF-beta 1 in the growth and progressive angiogenesis of the human glioma.
由于高级别原发性脑肿瘤显著的新生血管形成特征主要由血管平滑肌细胞（VSMC）构成，我们研究了强效平滑肌有丝分裂原内皮素-1（ET-1）及其一种促分泌素转化生长因子β1（TGF-β1）在一系列星形细胞瘤中的表达。TGF-β1因其作为血管生成因子的已知活性也备受关注。我们采用免疫组织化学方法检查了30例手术病例：10例多形性胶质母细胞瘤、10例间变性星形细胞瘤和10例低级别星形细胞瘤。使用抗TGF-β1单克隆抗体和抗ET-1多克隆抗体，我们在所有检查的胶质母细胞瘤病例中均检测到了这两种生长因子。在间变性星形细胞瘤病例中，4例肿瘤两种因子均呈阳性；2例仅含有ET-1；2例仅含有TGF-β1；2例对两种因子均无肿瘤细胞免疫反应性。在低级别星形细胞瘤中，10例肿瘤中有4例显示弱ET-1免疫反应性；其中2例含有TGF-β1免疫阳性的肿瘤星形细胞：6例肿瘤两种因子均为阴性。在所有表达两种因子的肿瘤中，连续切片显示ET-1免疫阳性区域也倾向于TGF-β1呈阳性。所有肿瘤内的内皮细胞ET-1均呈阳性。ET-1和TGF-β1存在于人类星形细胞瘤中，它们的表达与肿瘤血管生成和恶性程度相关。这些结果提示ET-1和TGF-β1在人类胶质瘤的生长和进行性血管生成中均发挥作用。
