Panobinostat suppresses the mesenchymal phenotype in a novel claudin-low triple negative patient-derived breast cancer model
Margarite D. Matossian 1, Hope E. Burks 1, Steven Elliott 1, Van T. Hoang 1, Annie C.Bowles 2, Rachel A. Sabol 2 Bruce A. Bunnell 2,3, Elizabeth C. Martin 4, Matthew E.Burow 1,3 and Bridgette M. Collins-Burow 1,5
1 Tulane University School of Medicine, Department of Medicine, Section of Hematology & Medical Oncology, New Orleans LA
2 Tulane Center for Stem Cell Research and Regenerative Medicine, New Orleans LA
3 Tulane University School of Medicine, Department of Pharmacology, New Orleans LA
4 Louisiana State University, Department of Agricultural Engineering, Baton Rouge LA
5 Tulane University School of Medicine, Tulane Cancer Center, New Orleans LA
Correspondence to:
Bridgette Collins-Burow, email: [email protected]
Keywords: Triple-negative breast cancer, claudin-low, patient-derived xenograft, histone deacetylase inhibitor, extracellular matrix
Received: January 31, 2018 Accepted: March 22, 2018 Published: April 29, 2018
Abstract
Claudin-low triple negative breast cancer (CL-TNBC) is a clinically aggressive molecular TNBC subtype characterized by a propensity to metastasize, recur and acquire chemoresistance. CL-TNBC has a diverse intra- and extracellular composition and microenvironment, and currently there are no clinically approved targeted therapies. Histone deacetylase inhibitors (HDACi) have been investigated as therapeutic agents targeting invasive TNBC phenotypes. However, further studies are required to evaluate HDAC inhibition in CL-TNBC. Here, we utilize a novel CLTNBC patient-derived xenograft model to study the various and diverse therapeutic potential targets within CL-TNBC tumors. To evaluate effects of the pan-HDACi panobinostat on metastasis and the mesenchymal phenotype of CL-TNBC, we utilize immunohistochemistry staining and qRT-PCR in in vitro, ex vivo and in vivo studies. Further, we evaluate pan-HDAC inhibition on stem-like subpopulations using 3D mammosphere culture techniques and quantification. Finally, we show that pan- HDACi suppresses collagen expression in CL-TNBC. In this study, we provide evidence that pan-HDAC inhibition has effects on various components of the CL-TNBC subtype, and we demonstrate the potential of our novel CL-TNBC PDX model in therapeutic discovery research.
PII: 412
