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Open AccessArticle

Profiling the Stromal and Vascular Heterogeneity in Patient-derived Xenograft Models of Head and Neck Cancer: Impact on Therapeutic Response

1
Department of Oral Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
2
Department of Pathology and Laboratory Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
3
Department of Otolaryngology, University of Pittsburgh—Hillman Cancer Center, Pittsburgh, PA 15261, USA
4
Department of Dentistry and Maxillofacial Prosthetics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(7), 951; https://doi.org/10.3390/cancers11070951
Received: 23 May 2019 / Revised: 25 June 2019 / Accepted: 28 June 2019 / Published: 6 July 2019
(This article belongs to the Special Issue Tumor Xenografts)
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PDF [12569 KB, uploaded 6 July 2019]
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Abstract

Head and neck squamous cell carcinomas (HNSCC) represent a group of epithelial neoplasms that exhibit considerable heterogeneity in clinical behavior. Here, we examined the stromal and vascular heterogeneity in a panel of patient-derived xenograft (PDX) models of HNSCC and the impact on therapeutic response. Tumor sections from established tumors were stained for p16 (surrogate for human papillomavirus (HPV) infection), stromal (Masson’s trichrome) and vascular (CD31) markers. All PDX models retained the HPV/p16 status of the original patient tumor. Immunohistochemical evaluation revealed the presence of multiple vessel phenotypes (tumor, stromal or mixed) in the PDX panel. Vascular phenotypes identified in the PDX models were validated in a tissue microarray of human HNSCC. Treatment with a microtubule targeted vascular disrupting agent (VDA) resulted in a heterogeneous antivascular and antitumor response in PDX models. The PDX with the tumor vessel phenotype that exhibited higher CD31+ vessel counts and leaky vasculature on magnetic resonance imaging (MRI) was sensitive to VDA treatment while the PDX with the stromal vessel phenotype was resistant to therapy. Collectively, our results demonstrate the phenotypic and functional vascular heterogeneity in HNSCC and highlight the impact of this heterogeneity on response to antivascular therapy in PDX models of HNSCC. View Full-Text
Keywords: patient derived xenografts; HNSCC; angiogenesis; heterogeneity; VDAs; MRI patient derived xenografts; HNSCC; angiogenesis; heterogeneity; VDAs; MRI
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Folaron, M.; Merzianu, M.; Duvvuri, U.; Ferris, R.L.; Seshadri, M. Profiling the Stromal and Vascular Heterogeneity in Patient-derived Xenograft Models of Head and Neck Cancer: Impact on Therapeutic Response. Cancers 2019, 11, 951.

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