Solberg H, Rømer J, Brünner N, Holm A, Sidenius N, Danø K, Høyer-Hansen G
Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.
Int J Cancer. 1994 Sep 15;58(6):877-81. doi: 10.1002/ijc.2910580622.
It was recently found that urokinase-type plasminogen activator (uPA) is involved in the cleavage of its receptor (uPAR) on cultured cells, thereby releasing one of the receptor's 3 domains (the ligand binding domain I) and leaving the 2 others [uPAR(2 + 3)] anchored to the cell surface. With monoclonal antibodies (MAbs) we have now identified human uPAR(2 + 3) in lysates of invasive human MDA-MB-231 mammary carcinomas xenografted into nude mice. The production of peptide antibodies recognizing different domains of murine uPAR made it possible to identify a similar cleaved form of uPAR, murine uPAR(2 + 3), in extracts of primary Lewis lung carcinomas. Cleavage of uPAR also occurs in cultured MDA-MB-231 cells and Lewis lung carcinoma cells. This cleavage is inhibited by anticatalytic antibodies to either human or murine uPA, respectively, indicating that it is catalyzed by either uPA or plasmin generated by uPA. The amount of uPAR(2 + 3) may therefore be directly related to the activity of the uPA system and it is possible that the level of uPAR(2 + 3) in cancer tissue may prove to be a stronger prognostic parameter than the levels of either full-length uPAR or UPA.
最近发现，尿激酶型纤溶酶原激活剂（uPA）参与其在培养细胞上的受体（uPAR）的裂解，从而释放受体的3个结构域之一（配体结合结构域I），而另外两个结构域[uPAR(2 + 3)]则锚定在细胞表面。我们现在用单克隆抗体（MAb）在移植到裸鼠体内的侵袭性人MDA-MB-231乳腺癌异种移植物的裂解物中鉴定出了人uPAR(2 + 3)。识别鼠uPAR不同结构域的肽抗体的产生使得在原发性Lewis肺癌提取物中鉴定出类似的裂解形式的uPAR，即鼠uPAR(2 + 3)成为可能。uPAR的裂解也发生在培养的MDA-MB-231细胞和Lewis肺癌细胞中。这种裂解分别被针对人或鼠uPA的抗催化抗体所抑制，这表明它是由uPA或uPA产生的纤溶酶催化的。因此，uPAR(2 + 3)的量可能与uPA系统的活性直接相关，并且癌症组织中uPAR(2 + 3)的水平可能被证明是比全长uPAR或UPA水平更强的预后参数。
