Lombardi P, Norata G, Maggi F M, Canti G, Franco P, Nicolin A, Catapano A L
Institute of Pharmacological Sciences, School of Pharmacy, Milan, Italy.
Biochim Biophys Acta. 1989 Jun 28;1003(3):301-6. doi: 10.1016/0005-2760(89)90236-1.
We have studied the uptake of 125I-labelled low-density lipoprotein (LDL) by seven experimental murine tumours in vivo. Four tumours (Lewis Lung carcinoma, B-16, MS-2 and Colon 26) showed a higher relative uptake of lipoprotein as compared to the liver, two (L-1210 and P-388) had a very low lipoprotein uptake, while lipoprotein uptake by tumour M5 was similar to that of the liver. The data was confirmed by tracing tissue uptake of lipoproteins using [14C]sucrose-labeled LDL. These in vivo findings correlated well with the in vitro specific binding of 125I-beta-VLDL to membranes prepared from tumours, thus suggesting that the expression of the LDL receptor in the tumours is related to the in vivo uptake of lipoprotein. Further analysis of the LDL receptor by ligand blotting showed that the tumor receptor has several of the liver LDL receptor characteristics (including apparent Mr, sensitivity to proteinases, and Ca2+ requirement of lipoprotein binding). In summary, our data show that experimental murine tumours express the LDL receptor and suggest that the high relative in vivo uptake of LDL is determined by the elevated LDL-receptor expression in the tumours.
我们研究了七种实验性小鼠肿瘤在体内对¹²⁵I标记的低密度脂蛋白（LDL）的摄取情况。与肝脏相比，四种肿瘤（Lewis肺癌、B-16、MS-2和结肠26）显示出较高的脂蛋白相对摄取量，两种肿瘤（L-1210和P-388）的脂蛋白摄取量非常低，而肿瘤M5的脂蛋白摄取量与肝脏相似。通过使用[¹⁴C]蔗糖标记的LDL追踪组织对脂蛋白的摄取，证实了这些数据。这些体内研究结果与¹²⁵I-β-VLDL与肿瘤制备的膜的体外特异性结合密切相关，因此表明肿瘤中LDL受体的表达与脂蛋白的体内摄取有关。通过配体印迹对LDL受体的进一步分析表明，肿瘤受体具有肝脏LDL受体的几个特征（包括表观分子量、对蛋白酶的敏感性以及脂蛋白结合对Ca²⁺的需求）。总之，我们的数据表明实验性小鼠肿瘤表达LDL受体，并表明LDL在体内的高相对摄取量是由肿瘤中LDL受体表达的升高所决定的。
