Albo D, Berger D H, Tuszynski G P
Department of Surgery, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania 19102, USA.
J Surg Res. 1998 Apr;76(1):86-90. doi: 10.1006/jsre.1998.5299.
We have previously shown that thrombospondin-1 (TSP-1) and TGF-beta 1 upregulate the urokinase plasminogen activator (uPA) and its receptor (uPAR) and promote tumor cell invasion in breast cancer. To date, the effect of TSP-1 and TGF-beta 1 on the plasminogen/plasmin system in gastrointestinal epithelial malignancies has not been investigated. In this study, we determined the effect of TSP-1 and TGF-beta 1 on uPA and uPAR expression and on tumor cell invasion in pancreatic cancer. ASPC1 human pancreatic adenocarcinoma cells were incubated for 48 h on cell-conditioned media (CCM) either alone (Control) or with the addition of either TSP-1 (40 micrograms/ml) or TGF-beta 1 (5 ng/ml). uPA and uPAR expression were determined by ELISA. ASPC1 cell invasion was determined in a modified Boyden chamber type I collagen invasion assay. The upper chamber was treated with CCM either alone (Control) or with the addition of anti-uPA (10 micrograms/ml) or anti-uPAR (10 micrograms/ml). The lower chamber was treated with CCM either alone (Control) or with the addition of either TSP-1 (40 micrograms/ml) or TGF-beta 1 (5 ng/ml). TSP-1 and TGF-beta 1 induced a twofold increase on uPAR expression but only a slight increase on total uPA. Tumor cell invasion was upregulated 3.5 to 4.5-fold by TSP-1 and TGF-beta 1, respectively. Anti-uPA and anti-uPAR antibodies completely blocked the TSP-1 and TGF-beta 1-mediated pancreatic tumor cell invasion. We conclude that TSP-1 and TGF-beta 1 mediate pancreatic tumor cell invasion through upregulation of the plasminogen/plasmin system.
我们之前已经表明，血小板反应蛋白-1（TSP-1）和转化生长因子-β1（TGF-β1）可上调尿激酶型纤溶酶原激活剂（uPA）及其受体（uPAR），并促进乳腺癌细胞的侵袭。迄今为止，尚未研究TSP-1和TGF-β1对胃肠道上皮恶性肿瘤中纤溶酶原/纤溶酶系统的影响。在本研究中，我们确定了TSP-1和TGF-β1对胰腺癌中uPA和uPAR表达以及肿瘤细胞侵袭的影响。将ASPC1人胰腺腺癌细胞在细胞条件培养基（CCM）上单独孵育48小时（对照），或添加TSP-1（40微克/毫升）或TGF-β1（5纳克/毫升）。通过酶联免疫吸附测定法（ELISA）测定uPA和uPAR的表达。在改良的博伊登小室I型胶原侵袭试验中测定ASPC1细胞的侵袭。上室单独用CCM处理（对照），或添加抗uPA（10微克/毫升）或抗uPAR（10微克/毫升）。下室单独用CCM处理（对照），或添加TSP-1（40微克/毫升）或TGF-β1（5纳克/毫升）。TSP-1和TGF-β1使uPAR表达增加两倍，但仅使总uPA略有增加。TSP-1和TGF-β1分别使肿瘤细胞侵袭上调3.5至4.5倍。抗uPA和抗uPAR抗体完全阻断了TSP-1和TGF-β1介导的胰腺肿瘤细胞侵袭。我们得出结论，TSP-1和TGF-β1通过上调纤溶酶原/纤溶酶系统介导胰腺肿瘤细胞侵袭。
