Yamamoto M, Sawaya R, Mohanam S, Loskutoff D J, Bruner J M, Rao V H, Oka K, Tomonaga M, Nicolson G L, Rao J S
Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Cancer Res. 1994 Jul 1;54(13):3329-32.
We investigated the expression and cellular localization of plasminogen activator inhibitor type 1 (PAI-1) in human astrocytoma in vivo. Northern blot and densitometric quantitation of PAI-1 mRNA indicated that PAI-1 transcripts were significantly higher in human malignant astrocytomas and especially in glioblastomas than in low-grade gliomas and normal brain tissues in vivo. Using in situ hybridization with paraffin-embedded surgical specimens of human gliomas and normal brain tissues, PAI-1 mRNA was abundantly expressed in glioblastomas. PAI-1 mRNA was localized mainly in tumor cells and endothelial cells. The distribution of PAI-1 mRNA expression was particularly abundant around areas of vascular proliferation and in remnant tumor cells surrounding necrotic foci. PAI-1 mRNA was also expressed in both the tumor and endothelial cells of anaplastic astrocytomas, whereas it was not expressed or only weakly expressed in low-grade astrocytomas or normal brain tissues. These results suggest that high expression of PAI-1 is associated with the malignant progression of astrocytic tumors and that excessive PAI-1 expression might be associated with intratumoral necrosis in glioblastomas.
我们在体内研究了纤溶酶原激活物抑制剂1型（PAI-1）在人星形细胞瘤中的表达及细胞定位。对PAI-1 mRNA进行Northern印迹和光密度定量分析表明，在体内，人恶性星形细胞瘤尤其是胶质母细胞瘤中的PAI-1转录物显著高于低级别胶质瘤和正常脑组织。利用原位杂交技术检测人胶质瘤和正常脑组织的石蜡包埋手术标本，发现胶质母细胞瘤中PAI-1 mRNA大量表达。PAI-1 mRNA主要定位于肿瘤细胞和内皮细胞。PAI-1 mRNA表达的分布在血管增生区域周围以及坏死灶周围的残留肿瘤细胞中尤为丰富。间变性星形细胞瘤的肿瘤细胞和内皮细胞中也表达PAI-1 mRNA，而在低级别星形细胞瘤或正常脑组织中不表达或仅微弱表达。这些结果表明，PAI-1的高表达与星形细胞瘤的恶性进展相关，并且PAI-1的过度表达可能与胶质母细胞瘤的瘤内坏死有关。
