Novel model for basaloid triple-negative breast cancer: behavior in vivo and response to therapy

LD Volk-Draper, S Rajput, KL Hall, A Wilber, S Rana - Neoplasia, 2012 - Elsevier
LD Volk-Draper, S Rajput, KL Hall, A Wilber, S Rana
Neoplasia, 2012Elsevier
Introduction: 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 …
Abstract
Introduction: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. Methods: 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. Results: 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%. Conclusions 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.
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