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

Folaron, Margaret and Merzianu, Mihai and Duvvuri, Umamaheswar and Ferris, Robert L. and Seshadri, Mukund (2019) Profiling the Stromal and Vascular Heterogeneity in Patient-derived Xenograft Models of Head and Neck Cancer: Impact on Therapeutic Response. Cancers, 11 (7). p. 951. ISSN 2072-6694

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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


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Folaron, Margaret
Merzianu, Mihai
Duvvuri, Umamaheswarumd3@pitt.eduumd3
Ferris, Robert
Seshadri, Mukund
Centers: Other Centers, Institutes, Offices, or Units > Hillman Cancer Center
Date: 9 July 2019
Date Type: Publication
Journal or Publication Title: Cancers
Volume: 11
Number: 7
Publisher: MDPI AG
Page Range: p. 951
DOI or Unique Handle: 10.3390/cancers11070951
Schools and Programs: School of Medicine > Otolaryngology
Refereed: Yes
Uncontrolled Keywords: patient derived xenografts, HNSCC, angiogenesis, heterogeneity, VDAs, MRI
ISSN: 2072-6694
Official URL:
Funders: National Institute of Health/ National Institute of Dental and Craniofacial Research, Roswell Park Alliance Foundation, Roswell Park Cancer Institute’s NCI-supported Core Grant
Article Type: Research Article
Date Deposited: 11 Jun 2021 20:38
Last Modified: 11 Jun 2021 20:38


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