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Clinical & Experimental Metastasis
Published in: Clinical & Experimental Metastasis 3/2020

01-06-2020 | Metastasis | Research Paper

Tumor shedding and metastatic progression after tumor excision in patient-derived orthotopic xenograft models of triple-negative breast cancer

Authors: Aryana M. Razmara, Elodie Sollier, Grace N. Kisirkoi, Sam W. Baker, Margot B. Bellon, Alex McMillan, Clementine A. Lemaire, Vishnu C. Ramani, Stefanie S. Jeffrey, Kerriann M. Casey

Published in: Clinical & Experimental Metastasis | Issue 3/2020

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Abstract

Patient-derived orthotopic xenograft (PDOX) models have been verified as a useful method for studying human cancers in mice. Previous studies on the extent of metastases in these models have been limited by the necessity of welfare euthanasia (primary tumors reaching threshold size), at which point metastases may only be micrometers in diameter, few in number, and solely identified by step-sectioning of formalin-fixed paraffin-embedded tissue. These small micro-metastases are less suitable for many downstream molecular analyses than macro-metastases. Resection of the primary tumor by survival surgery has been proven to allow further time for metastases to grow. Although PDOX models of triple-negative breast cancer (TNBC) shed circulating tumor cells (CTCs) into the bloodstream and metastasize, similar to human TNBC, little data has been collected in these TNBC PDOX models regarding the association between CTC characteristics and distant metastasis following excision of the primary tumor xenograft. This study assembles a timeline of PDOX tumor shedding and metastatic tumor progression before and after tumor excision surgery. We report the ability to use tumorectomies to increase the lifespan of TNBC PDOX models with the potential to obtain larger metastases. CTC clusters and CTCs expressing a mesenchymal marker (vimentin) were associated with metastatic burden in lung and liver. The data collected through these experiments will guide the further use of PDOX models in studying metastatic TNBC.
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Metadata
Title
Tumor shedding and metastatic progression after tumor excision in patient-derived orthotopic xenograft models of triple-negative breast cancer
Authors
Aryana M. Razmara
Elodie Sollier
Grace N. Kisirkoi
Sam W. Baker
Margot B. Bellon
Alex McMillan
Clementine A. Lemaire
Vishnu C. Ramani
Stefanie S. Jeffrey
Kerriann M. Casey
Publication date
01-06-2020
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 3/2020
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-020-10033-3

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