Michalides R, Kwa B, Springall D, van Zandwijk N, Koopman J, Hilkens J, Mooi W
Department of Tumor Biology, The Netherlands Cancer Institute, Amsterdam.
Int J Cancer Suppl. 1994;8:34-7. doi: 10.1002/ijc.2910570707.
The presence of the neural cell adhesion molecule, NCAM, is indicative for a poor prognosis in lung-cancer patients. Using MAb 735, we have investigated the expression of polysialic acid, PSA, on NCAM in a spectrum of neuro-endocrine lung tumors, ranging from the slowly growing typical carcinoids via the atypical carcinoids with clinically unpredictable behavior to the highly aggressive small-cell lung carcinomas. Our immunohistochemical findings indicate a significant association between the presence of PSA on the tumor cells and an aggressive and immature sub-type of the tumor. This might be related to impairment of cell-cell and cell-matrix interactions by the presence of PSA, as we demonstrated in vitro, since detachment is one of the first steps in the metastatic process. The NCAM-MAb 123C3 used in these studies appeared extremely useful in immunoscintigraphy and immunotherapy of SCLC xenografts in nude mice, and for immunoscintigraphy of a SCLC patient. This may be explained by internalization of the 123C3 antibody, which we demonstrated in vitro. 123C3 is the only Cluster-I SCLC MAb studied thus far that becomes internalized.
神经细胞黏附分子(NCAM)的存在表明肺癌患者预后不良。我们使用单克隆抗体735(MAb 735),研究了多唾液酸(PSA)在一系列神经内分泌性肺肿瘤的NCAM上的表达情况,这些肿瘤包括生长缓慢的典型类癌、具有临床不可预测行为的非典型类癌以及侵袭性很强的小细胞肺癌。我们的免疫组化结果表明,肿瘤细胞上PSA的存在与肿瘤的侵袭性和不成熟亚型之间存在显著关联。这可能与PSA的存在导致细胞间和细胞与基质相互作用受损有关,正如我们在体外所证明的,因为脱离是转移过程的第一步。这些研究中使用的NCAM单克隆抗体123C3在裸鼠小细胞肺癌异种移植瘤的免疫闪烁显像和免疫治疗以及一名小细胞肺癌患者的免疫闪烁显像中似乎非常有用。这可能是由于123C3抗体的内化作用,这是我们在体外证明的。123C3是迄今为止研究的唯一一种会发生内化的第一类小细胞肺癌单克隆抗体。