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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2018
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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. |
format | Online Article Text |
id | pubmed-5835943 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
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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