Rowland-Goldsmith Melissa A, Maruyama Haruhisa, Matsuda Kei, Idezawa Takenao, Ralli Monica, Ralli Sonia, Korc Murray
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Biological Chemistry, and Pharmacology, University of California, Irvine, California 92697, USA.
Mol Cancer Ther. 2002 Jan;1(3):161-7.
Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that frequently metastasizes and that overexpresses transforming growth factor-beta s (TGF-beta s). To determine whether TGF-beta s can act to enhance the metastatic potential of PDAC, PANC-1 human pancreatic cancer cells were transfected with an expression construct encoding a soluble type II TGF-beta receptor (sT beta RII) that blocks cellular responsiveness to TGF-beta 1. When injected s.c. in athymic mice, PANC-1 clones expressing sT beta RII exhibited decreased tumor growth in comparison with sham-transfected cells and attenuated expression of plasminogen activator inhibitor 1 (PAI-1), a gene associated with tumor growth. When tested in an orthotopic mouse model, these clones formed small intrapancreatic tumors that exhibited a suppressed metastatic capacity and decreased expression of plasminogen activator inhibitor 1 and the metastasis-associated urokinase plasminogen activator. These results indicate that TGF-beta s act in vivo to enhance the expression of genes that promote the growth and metastasis of pancreatic cancer cells and suggest that sT beta RII may ultimately have a therapeutic benefit in PDAC.
胰腺导管腺癌（PDAC）是一种致命的恶性肿瘤，常发生转移且过度表达转化生长因子-β（TGF-β）。为了确定TGF-β是否能增强PDAC的转移潜能，用编码可溶性II型TGF-β受体（sTβRII）的表达构建体转染PANC-1人胰腺癌细胞，该受体可阻断细胞对TGF-β1的反应。当将表达sTβRII的PANC-1克隆皮下注射到无胸腺小鼠体内时，与假转染细胞相比，其肿瘤生长减缓，且纤溶酶原激活物抑制剂1（PAI-1）的表达减弱，PAI-1是一种与肿瘤生长相关的基因。在原位小鼠模型中进行测试时，这些克隆形成的胰腺内小肿瘤转移能力受到抑制，纤溶酶原激活物抑制剂1和转移相关的尿激酶型纤溶酶原激活物的表达降低。这些结果表明，TGF-β在体内可增强促进胰腺癌细胞生长和转移的基因的表达，并提示sTβRII最终可能对PDAC具有治疗益处。
