Barok Márk, Balázs Margit, Nagy Péter, Rákosy Zsuzsa, Treszl Andrea, Tóth Eniko, Juhász István, Park John W, Isola Jorma, Vereb György, Szöllosi János
Department of Biophysics and Cell Biology, University of Debrecen, 4012 Debrecen, Egyetem ter 1., Hungary.
Cancer Lett. 2008 Feb 18;260(1-2):198-208. doi: 10.1016/j.canlet.2007.10.043. Epub 2007 Dec 21.
We have recently shown that despite of the fact that the ErbB2-positive JIMT-1 human breast cancer cells intrinsically resistant to trastuzumab in vitro, trastuzumab inhibited the outgrowth of early phase JIMT-1 xenografts in SCID mice via antibody-dependent cellular cytotoxicity (ADCC). Here we show that trastuzumab significantly reduces the number of circulating and disseminated tumor cells (CTCs and DTCs) in this xenograft model system at a time when the primary tumor is already unresponsive to trastuzumab. This observation suggests that ErbB2 positive CTCs and DTCs might be sensitive to trastuzumab-mediated ADCC even if when the primary tumor is already non-responsive. Thus, trastuzumab treatment might also be beneficial in the case of patients with breast cancer that is already trastuzumab resistant.
我们最近发现,尽管ErbB2阳性的JIMT-1人乳腺癌细胞在体外对曲妥珠单抗具有内在抗性,但曲妥珠单抗通过抗体依赖性细胞毒性(ADCC)抑制了SCID小鼠体内早期JIMT-1异种移植物的生长。在此我们表明,在原发性肿瘤已对曲妥珠单抗无反应时,曲妥珠单抗在该异种移植模型系统中显著减少了循环肿瘤细胞和播散肿瘤细胞(CTC和DTC)的数量。这一观察结果表明,即使原发性肿瘤已无反应,ErbB2阳性的CTC和DTC可能对曲妥珠单抗介导的ADCC敏感。因此,对于已经对曲妥珠单抗耐药的乳腺癌患者,曲妥珠单抗治疗可能也有益处。