Hypoxia Patterns in Primary and Metastatic Prostate Cancer Environments
Metastatic dissemination continues to be a major cause of prostate cancer (PCa) mortality, creating a compelling need to understand factors that play a role in the metastatic cascade. Since hypoxia plays an important role in PCa aggressiveness, we characterized patterns of hypoxia in the primary tum...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2019-02-01
|
Series: | Neoplasia: An International Journal for Oncology Research |
Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558618305578 |
id |
doaj-805fae394954438d926c4b84f4035c50 |
---|---|
record_format |
Article |
spelling |
doaj-805fae394954438d926c4b84f4035c502020-11-24T21:59:53ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862019-02-01212239246Hypoxia Patterns in Primary and Metastatic Prostate Cancer EnvironmentsSantosh Kumar Bharti0Samata Kakkad1Pierre Danhier2Flonne Wildes3Marie-France Penet4Balaji Krishnamachary5Zaver M. Bhujwalla6Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USADivision of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USADivision of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USADivision of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USADivision of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine; Baltimore, MD, USADivision of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USADivision of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine; Baltimore, MD, USA; Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Address all correspondence to: Zaver M. Bhujwalla, PhD, The Johns Hopkins University School of Medicine, 208C Traylor Building, 720 Rutland Avenue, Baltimore, MD 21205, USA.Metastatic dissemination continues to be a major cause of prostate cancer (PCa) mortality, creating a compelling need to understand factors that play a role in the metastatic cascade. Since hypoxia plays an important role in PCa aggressiveness, we characterized patterns of hypoxia in the primary tumor and metastatic environments of a human PCa xenograft. We previously developed and characterized an imaging strategy based on the hypoxia response element (HRE)–driven expression of long-lived enhanced green fluorescent protein (EGFP) and short-lived luciferase (luc) fused to the oxygen-dependent degradation domain in human PCa PC-3 cells. Both reporter proteins were placed under the transcriptional control of a five–tandem repeat HRE sequence. PC-3 cells also constitutively expressed the tdTomato red fluorescent protein, allowing cancer cell detection in vivo. This “timer” strategy can provide information on the temporal evolution of HIF activity and hypoxia in tumors. Here, for the first time, we performed in vivo and ex vivo imaging of this dual HIF reporter system in PC-3 metastatic tumors implanted orthotopically in the prostate and PC-3 nonmetastatic tumors implanted subcutaneously. We observed distinct patterns of EGFP and luc expression in subcutaneous and orthotopic tumors, and in metastatic nodules, that provide new insights into the presence of hypoxia at primary and metastatic tumor sites, and of the role of hypoxia in metastasis.http://www.sciencedirect.com/science/article/pii/S1476558618305578 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Santosh Kumar Bharti Samata Kakkad Pierre Danhier Flonne Wildes Marie-France Penet Balaji Krishnamachary Zaver M. Bhujwalla |
spellingShingle |
Santosh Kumar Bharti Samata Kakkad Pierre Danhier Flonne Wildes Marie-France Penet Balaji Krishnamachary Zaver M. Bhujwalla Hypoxia Patterns in Primary and Metastatic Prostate Cancer Environments Neoplasia: An International Journal for Oncology Research |
author_facet |
Santosh Kumar Bharti Samata Kakkad Pierre Danhier Flonne Wildes Marie-France Penet Balaji Krishnamachary Zaver M. Bhujwalla |
author_sort |
Santosh Kumar Bharti |
title |
Hypoxia Patterns in Primary and Metastatic Prostate Cancer Environments |
title_short |
Hypoxia Patterns in Primary and Metastatic Prostate Cancer Environments |
title_full |
Hypoxia Patterns in Primary and Metastatic Prostate Cancer Environments |
title_fullStr |
Hypoxia Patterns in Primary and Metastatic Prostate Cancer Environments |
title_full_unstemmed |
Hypoxia Patterns in Primary and Metastatic Prostate Cancer Environments |
title_sort |
hypoxia patterns in primary and metastatic prostate cancer environments |
publisher |
Elsevier |
series |
Neoplasia: An International Journal for Oncology Research |
issn |
1476-5586 |
publishDate |
2019-02-01 |
description |
Metastatic dissemination continues to be a major cause of prostate cancer (PCa) mortality, creating a compelling need to understand factors that play a role in the metastatic cascade. Since hypoxia plays an important role in PCa aggressiveness, we characterized patterns of hypoxia in the primary tumor and metastatic environments of a human PCa xenograft. We previously developed and characterized an imaging strategy based on the hypoxia response element (HRE)–driven expression of long-lived enhanced green fluorescent protein (EGFP) and short-lived luciferase (luc) fused to the oxygen-dependent degradation domain in human PCa PC-3 cells. Both reporter proteins were placed under the transcriptional control of a five–tandem repeat HRE sequence. PC-3 cells also constitutively expressed the tdTomato red fluorescent protein, allowing cancer cell detection in vivo. This “timer” strategy can provide information on the temporal evolution of HIF activity and hypoxia in tumors. Here, for the first time, we performed in vivo and ex vivo imaging of this dual HIF reporter system in PC-3 metastatic tumors implanted orthotopically in the prostate and PC-3 nonmetastatic tumors implanted subcutaneously. We observed distinct patterns of EGFP and luc expression in subcutaneous and orthotopic tumors, and in metastatic nodules, that provide new insights into the presence of hypoxia at primary and metastatic tumor sites, and of the role of hypoxia in metastasis. |
url |
http://www.sciencedirect.com/science/article/pii/S1476558618305578 |
work_keys_str_mv |
AT santoshkumarbharti hypoxiapatternsinprimaryandmetastaticprostatecancerenvironments AT samatakakkad hypoxiapatternsinprimaryandmetastaticprostatecancerenvironments AT pierredanhier hypoxiapatternsinprimaryandmetastaticprostatecancerenvironments AT flonnewildes hypoxiapatternsinprimaryandmetastaticprostatecancerenvironments AT mariefrancepenet hypoxiapatternsinprimaryandmetastaticprostatecancerenvironments AT balajikrishnamachary hypoxiapatternsinprimaryandmetastaticprostatecancerenvironments AT zavermbhujwalla hypoxiapatternsinprimaryandmetastaticprostatecancerenvironments |
_version_ |
1725846759084654592 |