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Cancer-associated fibroblasts enhance tumor (18)F-FDG uptake and contribute to the intratumor heterogeneity of PET-CT

Purpose: Elevated glucose uptake is a hallmark of cancer. Fluorodeoxyglucose (FDG) uptake was believed to indicate the aggressiveness of tumors and the standardized uptake value (SUV) is a well-known measurement for FDG uptake in positron emission tomography-computed tomography (PET/CT). However, th...

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Autores principales: Shangguan, Chengfang, Gan, Guifang, Zhang, Jieying, Wu, Jinliang, Miao, Ying, Zhang, Miao, Li, Biao, Mi, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835943/
https://www.ncbi.nlm.nih.gov/pubmed/29507627
http://dx.doi.org/10.7150/thno.22717
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author Shangguan, Chengfang
Gan, Guifang
Zhang, Jieying
Wu, Jinliang
Miao, Ying
Zhang, Miao
Li, Biao
Mi, Jun
author_facet Shangguan, Chengfang
Gan, Guifang
Zhang, Jieying
Wu, Jinliang
Miao, Ying
Zhang, Miao
Li, Biao
Mi, Jun
author_sort Shangguan, Chengfang
collection PubMed
description Purpose: Elevated glucose uptake is a hallmark of cancer. Fluorodeoxyglucose (FDG) uptake was believed to indicate the aggressiveness of tumors and the standardized uptake value (SUV) is a well-known measurement for FDG uptake in positron emission tomography-computed tomography (PET/CT). However, the SUV is variable due to the heterogeneity of tumors. Methods: 126 patients with colorectal cancer underwent (18)F-FDG PET/CT scanning before surgery between Jan 2011 and April 2016. Cancer-associated fibroblast (CAF) densities were calculated with the inForm Advanced image analysis software and were comparatively analyzed between patients with high and low maximum SUV (SUVmax-high and SUVmax-low). Glucose uptake was evaluated in induced and isolated CAFs and CAF-cocultured colon cancer HCT116 cells. Moreover, micro-PET/CT was performed on xenografted tumors and autoradiography was performed in the AOM/DSS induced colon cancer model. Results: CAFs were glycolytic, evidenced by glucose uptake and upregulated HK2 expression. Compared to non-activated fibroblasts (NAFs), CAFs were more dependent on glucose and sensitive to a glycolysis inhibitor. CAFs increased the SUVmax in xenograft tumors and spontaneous colon cancers. Moreover, multivariate analysis revealed that the SUVmax was only associated with tumor size among conventional parameters in colon cancer patients (126 cases, p = 0.009). Besides tumor size, the CAF density was the critical factor associated with SUVmax and outcome, which was 2.27 ± 0.74 and 1.68 ± 0.45 in the SUVmax-high and the SUVmax-low groups, respectively (p = 0.014). Conclusion: CAFs promote tumor progression and increase SUVmax of (18)F-FDG, suggesting CAFs lead to the intratumor heterogeneity of the SUV and the SUVmax is a prognostic marker for cancer patients.
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spelling pubmed-58359432018-03-05 Cancer-associated fibroblasts enhance tumor (18)F-FDG uptake and contribute to the intratumor heterogeneity of PET-CT Shangguan, Chengfang Gan, Guifang Zhang, Jieying Wu, Jinliang Miao, Ying Zhang, Miao Li, Biao Mi, Jun Theranostics Research Paper Purpose: Elevated glucose uptake is a hallmark of cancer. Fluorodeoxyglucose (FDG) uptake was believed to indicate the aggressiveness of tumors and the standardized uptake value (SUV) is a well-known measurement for FDG uptake in positron emission tomography-computed tomography (PET/CT). However, the SUV is variable due to the heterogeneity of tumors. Methods: 126 patients with colorectal cancer underwent (18)F-FDG PET/CT scanning before surgery between Jan 2011 and April 2016. Cancer-associated fibroblast (CAF) densities were calculated with the inForm Advanced image analysis software and were comparatively analyzed between patients with high and low maximum SUV (SUVmax-high and SUVmax-low). Glucose uptake was evaluated in induced and isolated CAFs and CAF-cocultured colon cancer HCT116 cells. Moreover, micro-PET/CT was performed on xenografted tumors and autoradiography was performed in the AOM/DSS induced colon cancer model. Results: CAFs were glycolytic, evidenced by glucose uptake and upregulated HK2 expression. Compared to non-activated fibroblasts (NAFs), CAFs were more dependent on glucose and sensitive to a glycolysis inhibitor. CAFs increased the SUVmax in xenograft tumors and spontaneous colon cancers. Moreover, multivariate analysis revealed that the SUVmax was only associated with tumor size among conventional parameters in colon cancer patients (126 cases, p = 0.009). Besides tumor size, the CAF density was the critical factor associated with SUVmax and outcome, which was 2.27 ± 0.74 and 1.68 ± 0.45 in the SUVmax-high and the SUVmax-low groups, respectively (p = 0.014). Conclusion: CAFs promote tumor progression and increase SUVmax of (18)F-FDG, suggesting CAFs lead to the intratumor heterogeneity of the SUV and the SUVmax is a prognostic marker for cancer patients. Ivyspring International Publisher 2018-02-02 /pmc/articles/PMC5835943/ /pubmed/29507627 http://dx.doi.org/10.7150/thno.22717 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Shangguan, Chengfang
Gan, Guifang
Zhang, Jieying
Wu, Jinliang
Miao, Ying
Zhang, Miao
Li, Biao
Mi, Jun
Cancer-associated fibroblasts enhance tumor (18)F-FDG uptake and contribute to the intratumor heterogeneity of PET-CT
title Cancer-associated fibroblasts enhance tumor (18)F-FDG uptake and contribute to the intratumor heterogeneity of PET-CT
title_full Cancer-associated fibroblasts enhance tumor (18)F-FDG uptake and contribute to the intratumor heterogeneity of PET-CT
title_fullStr Cancer-associated fibroblasts enhance tumor (18)F-FDG uptake and contribute to the intratumor heterogeneity of PET-CT
title_full_unstemmed Cancer-associated fibroblasts enhance tumor (18)F-FDG uptake and contribute to the intratumor heterogeneity of PET-CT
title_short Cancer-associated fibroblasts enhance tumor (18)F-FDG uptake and contribute to the intratumor heterogeneity of PET-CT
title_sort cancer-associated fibroblasts enhance tumor (18)f-fdg uptake and contribute to the intratumor heterogeneity of pet-ct
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835943/
https://www.ncbi.nlm.nih.gov/pubmed/29507627
http://dx.doi.org/10.7150/thno.22717
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