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Comparison of tumor angiogenesis in subcutaneous and orthotopic LNCaP mouse models using contrast-enhanced ultrasound imaging

BACKGROUND: Understanding angiogenesis in prostate cancer is essential. LNCaP prostate xenograft tumors are androgen responsive and closely mimic clinical disease. Orthotopic animal models replicate aspects of the cancer microenvironment and are more clinically relevant than subcutaneous models. Com...

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Autores principales: Liu, Weiyong, Zhu, Yunkai, Ye, Lei, Zhu, Yajuan, Wang, Yuhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797366/
https://www.ncbi.nlm.nih.gov/pubmed/35116633
http://dx.doi.org/10.21037/tcr-21-372
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author Liu, Weiyong
Zhu, Yunkai
Ye, Lei
Zhu, Yajuan
Wang, Yuhao
author_facet Liu, Weiyong
Zhu, Yunkai
Ye, Lei
Zhu, Yajuan
Wang, Yuhao
author_sort Liu, Weiyong
collection PubMed
description BACKGROUND: Understanding angiogenesis in prostate cancer is essential. LNCaP prostate xenograft tumors are androgen responsive and closely mimic clinical disease. Orthotopic animal models replicate aspects of the cancer microenvironment and are more clinically relevant than subcutaneous models. Comparative studies investigating angiogenesis using contrast-enhanced ultrasound (CEUS) imaging in subcutaneous and orthotopic mouse models of prostate cancer have not been performed. METHODS: Tumor microcirculation and perfusion in subcutaneous and orthotopic LNCaP xenograft Balb/c athymic nude mice models were compared by investigating microbubble wash-in with CEUS. RESULTS: The take rate of subcutaneous and orthotopic tumors were 58.3% and 68.2%, respectively. On CEUS, orthotopic prostate tumors enhanced more rapidly than subcutaneous tumors. Mean arrival-time (Atm) for subcutaneous tumors, orthotopic prostate tumors, and kidney were 4.21±1.86, 1.72±0.79, and 0.73±0.12 s, respectively. Mean Atm was significantly longer for subcutaneous tumors compared to orthotopic prostate tumors or kidney (P<0.01). Mean time to peak enhancement (TtoPk) for subcutaneous tumors, orthotopic prostate tumors, and kidney were 38.56±13.23, 12.39±7.17, and 3.74±1.41 s, respectively. Mean TtoPk were significantly shorter for orthotopic prostate tumors and kidney compared to subcutaneous tumors (P<0.01). Mean wash-in area under the curve (WiAuC) for subcutaneous tumors, orthotopic prostate tumors, and kidney were 611.11±247.52, 1,800.57±623.11, and 1,887.51±103.68 dB, respectively. Mean AUC was significantly higher for orthotopic prostate tumors and kidney compared to subcutaneous tumors (P<0.01). Parametric imaging confirmed these findings. The density of CD31-positive vessels was significantly higher in orthotopic prostate tumors (43.98±6.14 vessels/field) compared to subcutaneous tumors (15.44±3.74 vessels/field, P<0.01). CONCLUSIONS: These findings demonstrate that orthotopic LNCaP xenografts better recreate a pro-angiogenic microenvironment than subcutaneous LNCaP xenografts.
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spelling pubmed-87973662022-02-02 Comparison of tumor angiogenesis in subcutaneous and orthotopic LNCaP mouse models using contrast-enhanced ultrasound imaging Liu, Weiyong Zhu, Yunkai Ye, Lei Zhu, Yajuan Wang, Yuhao Transl Cancer Res Original Article BACKGROUND: Understanding angiogenesis in prostate cancer is essential. LNCaP prostate xenograft tumors are androgen responsive and closely mimic clinical disease. Orthotopic animal models replicate aspects of the cancer microenvironment and are more clinically relevant than subcutaneous models. Comparative studies investigating angiogenesis using contrast-enhanced ultrasound (CEUS) imaging in subcutaneous and orthotopic mouse models of prostate cancer have not been performed. METHODS: Tumor microcirculation and perfusion in subcutaneous and orthotopic LNCaP xenograft Balb/c athymic nude mice models were compared by investigating microbubble wash-in with CEUS. RESULTS: The take rate of subcutaneous and orthotopic tumors were 58.3% and 68.2%, respectively. On CEUS, orthotopic prostate tumors enhanced more rapidly than subcutaneous tumors. Mean arrival-time (Atm) for subcutaneous tumors, orthotopic prostate tumors, and kidney were 4.21±1.86, 1.72±0.79, and 0.73±0.12 s, respectively. Mean Atm was significantly longer for subcutaneous tumors compared to orthotopic prostate tumors or kidney (P<0.01). Mean time to peak enhancement (TtoPk) for subcutaneous tumors, orthotopic prostate tumors, and kidney were 38.56±13.23, 12.39±7.17, and 3.74±1.41 s, respectively. Mean TtoPk were significantly shorter for orthotopic prostate tumors and kidney compared to subcutaneous tumors (P<0.01). Mean wash-in area under the curve (WiAuC) for subcutaneous tumors, orthotopic prostate tumors, and kidney were 611.11±247.52, 1,800.57±623.11, and 1,887.51±103.68 dB, respectively. Mean AUC was significantly higher for orthotopic prostate tumors and kidney compared to subcutaneous tumors (P<0.01). Parametric imaging confirmed these findings. The density of CD31-positive vessels was significantly higher in orthotopic prostate tumors (43.98±6.14 vessels/field) compared to subcutaneous tumors (15.44±3.74 vessels/field, P<0.01). CONCLUSIONS: These findings demonstrate that orthotopic LNCaP xenografts better recreate a pro-angiogenic microenvironment than subcutaneous LNCaP xenografts. AME Publishing Company 2021-07 /pmc/articles/PMC8797366/ /pubmed/35116633 http://dx.doi.org/10.21037/tcr-21-372 Text en 2021 Translational Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
spellingShingle Original Article
Liu, Weiyong
Zhu, Yunkai
Ye, Lei
Zhu, Yajuan
Wang, Yuhao
Comparison of tumor angiogenesis in subcutaneous and orthotopic LNCaP mouse models using contrast-enhanced ultrasound imaging
title Comparison of tumor angiogenesis in subcutaneous and orthotopic LNCaP mouse models using contrast-enhanced ultrasound imaging
title_full Comparison of tumor angiogenesis in subcutaneous and orthotopic LNCaP mouse models using contrast-enhanced ultrasound imaging
title_fullStr Comparison of tumor angiogenesis in subcutaneous and orthotopic LNCaP mouse models using contrast-enhanced ultrasound imaging
title_full_unstemmed Comparison of tumor angiogenesis in subcutaneous and orthotopic LNCaP mouse models using contrast-enhanced ultrasound imaging
title_short Comparison of tumor angiogenesis in subcutaneous and orthotopic LNCaP mouse models using contrast-enhanced ultrasound imaging
title_sort comparison of tumor angiogenesis in subcutaneous and orthotopic lncap mouse models using contrast-enhanced ultrasound imaging
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797366/
https://www.ncbi.nlm.nih.gov/pubmed/35116633
http://dx.doi.org/10.21037/tcr-21-372
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