Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Institute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany.
EMBO Mol Med. 2020 Sep 7;12(9):e11908. doi: 10.15252/emmm.201911908. Epub 2020 Jul 15.
Functional studies giving insight into the biology of circulating tumor cells (CTCs) remain scarce due to the low frequency of CTCs and lack of appropriate models. Here, we describe the characterization of a novel CTC-derived breast cancer cell line, designated CTC-ITB-01, established from a patient with metastatic estrogen receptor-positive (ER ) breast cancer, resistant to endocrine therapy. CTC-ITB-01 remained ER in culture, and copy number alteration (CNA) profiling showed high concordance between CTC-ITB-01 and CTCs originally present in the patient with cancer at the time point of blood draw. RNA-sequencing data indicate that CTC-ITB-01 has a predominantly epithelial expression signature. Primary tumor and metastasis formation in an intraductal PDX mouse model mirrored the clinical progression of ER breast cancer. Downstream ER signaling was constitutively active in CTC-ITB-01 independent of ligand availability, and the CDK4/6 inhibitor Palbociclib strongly inhibited CTC-ITB-01 growth. Thus, we established a functional model that opens a new avenue to study CTC biology.
由于循环肿瘤细胞 (CTC) 的频率较低且缺乏合适的模型，因此深入了解其生物学功能的研究仍然很少。在这里，我们描述了一种新型 CTC 衍生的乳腺癌细胞系 CTC-ITB-01 的特征，该细胞系从一名转移性雌激素受体阳性 (ER) 乳腺癌患者中建立，该患者对内分泌治疗耐药。在培养过程中，CTC-ITB-01 仍保持 ER 状态，拷贝数改变 (CNA) 分析显示 CTC-ITB-01 与患者癌症时采血点的 CTC 之间具有高度一致性。RNA-seq 数据表明 CTC-ITB-01 具有主要的上皮表达特征。在一个腔内 PDX 小鼠模型中，原发肿瘤和转移的形成反映了 ER 乳腺癌的临床进展。下游 ER 信号在 CTC-ITB-01 中独立于配体的可用性而持续激活，CDK4/6 抑制剂 Palbociclib 强烈抑制 CTC-ITB-01 的生长。因此，我们建立了一个功能模型，为研究 CTC 生物学开辟了新途径。
