Department of Medical Microbiology, Southern Illinois University School of Medicine, Springfield, IL 62794-9626, USA.
Neoplasia. 2012 Oct;14(10):926-42. doi: 10.1593/neo.12956.
The basaloid triple-negative breast cancer (B-TNBC) is one of the most aggressive, therapy-resistant, and metastatic tumors. Current models do not recapitulate the basaloid phenotype of TNBC, thus limiting the understanding of its biology and designing new treatments. We identified HCC1806 as a line expressing typical B-TNBC markers, engineered a subline with traceable reporters, and determined growth, drug sensitivity, recurrence, and vascular and metastatic patterns of orthotopic xenografts in immunodeficient mice.
mRNA and protein analyses showed that HCC1806 expresses basal but not luminal or mesenchymal markers. HCC1806-RR subline stably expressing red fluorescent protein and Renilla luciferase was generated and characterized for sensitivity to chemodrugs, orthotopic growth, vascular properties, recurrence, metastasis, and responsiveness in vivo.
The HCC1806 cells were highly sensitive to paclitaxel, but cytotoxicity was accompanied by pro-survival vascular endothelial growth factor-A loop. In vivo, HCC1806-RR tumors display linear growth, induce peritumoral lymphatics, and spontaneously metastasize to lymph nodes (LNs) and lungs. Similarly to human B-TNBC, HCC1806-RR tumors were initially sensitive to taxane therapy but subsequently recur. Bevacizumab significantly suppressed recurrence by 50% and reduced the incidence of LN and pulmonary metastases by, respectively, 50% and 87%.
The HCC1806-RR is a new model that expresses bona fide markers of B-TNBC and traceable markers for quantifying metastases. Combination of bevacizumab with nab-paclitaxel significantly improved the outcome, suggesting that this approach can apply to human patients with B-TNBC. This model can be used for defining the metastatic mechanisms of B-TNBC and testing new therapies.
基底细胞三阴性乳腺癌（B-TNBC）是最具侵袭性、耐药性和转移性的肿瘤之一。目前的模型无法重现 TNBC 的基底样表型，从而限制了对其生物学的理解和新治疗方法的设计。我们鉴定出 HCC1806 是一种表达典型 B-TNBC 标志物的细胞系，构建了一个带有可追踪报告基因的亚系，并确定了其在免疫缺陷小鼠中的原位异种移植的生长、药物敏感性、复发以及血管和转移模式。
mRNA 和蛋白质分析表明，HCC1806 表达基底而非腔面或间充质标志物。我们生成并表征了稳定表达红色荧光蛋白和 Renilla 荧光素酶的 HCC1806-RR 亚系，以评估其对化疗药物的敏感性、原位生长、血管特性、复发、转移以及体内的响应性。
HCC1806 细胞对紫杉醇高度敏感，但细胞毒性伴随着促生存的血管内皮生长因子-A 循环。在体内，HCC1806-RR 肿瘤呈线性生长，诱导肿瘤周围淋巴管，并自发转移至淋巴结（LNs）和肺部。与人类 B-TNBC 相似，HCC1806-RR 肿瘤最初对紫杉烷治疗敏感，但随后复发。贝伐珠单抗可使复发率降低 50%，淋巴结和肺部转移的发生率分别降低 50%和 87%。
HCC1806-RR 是一种新的模型，表达真正的 B-TNBC 标志物和可追踪的转移标志物。贝伐珠单抗联合 nab-紫杉醇显著改善了预后，表明该方法可应用于人类 B-TNBC 患者。该模型可用于定义 B-TNBC 的转移机制并测试新疗法。
