Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells

Chunwei Peng,1 Jiuyang Liu,1 Guifang Yang,2 Yan Li3 1Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, 2Department of Pathology, Zhongnan Hospital of Wuhan University, Wucha...

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Autores principales:	Peng CW, Liu JY, Yang GF, Li Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Quantum dots Cancer stromal Multiplexed molecular imaging Nanomedicine Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/414f7f0c63e744988185ebf33ef8c040
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spelling	oai:doaj.org-article:414f7f0c63e744988185ebf33ef8c0402021-12-02T07:20:21ZLysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells1178-2013https://doaj.org/article/414f7f0c63e744988185ebf33ef8c0402017-12-01T00:00:00Zhttps://www.dovepress.com/lysyl-oxidase-activates-cancer-stromal-cells-and-promotes-gastric-canc-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Chunwei Peng,1 Jiuyang Liu,1 Guifang Yang,2 Yan Li3 1Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, 2Department of Pathology, Zhongnan Hospital of Wuhan University, Wuchang District, Wuhan, 3Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital Affiliated to the Capital Medical University, Yangfangdian, Beijing, People’s Republic of China Purpose: Semiconductor quantum dots (QDs) are a promising alternative to organic fluorescent dyes for multiplexed molecular imaging of cancer stroma, which have great advantages in holistically analyzing the complex interactions among cancer stromal components in situ.Patients and methods: A QD probe-based multiplexed spectral molecular imaging method was established for simultaneous imaging. Three tissue microarrays (TMAs) including 184 gastric cancer (GC) tissues were constructed for the study. Multispectral analyses were performed for quantifying stromal biomarkers, such as lysyl oxidase (LOX). The stromal status including infiltrating of immune cells (high density of macrophages), angiogenesis (high density of microvessel density [MVD], low neovessel maturation) and extracellular matrix (ECM) remodeling (low density of type IV collagen, intense expression of matrix metalloproteinase 9 [MMP-9]) was evaluated.Results: This study compared the imaging features of the QD probe-based single molecular imaging method, immunohistochemistry, and organic dye-based immunofluorescent methods, and showed the advantages of the QD probe-based multiple molecular imaging method for simultaneously visualizing complex components of cancer stroma. The risk of macrophages in high density, high MVD, low neomicrovessel maturation, MMP-9 expression and low type IV collagen was significantly increased for the expression of LOX. With the advantages of the established QD probe-based multiplexed molecular imaging method, the spatial relationship between LOX and stromal essential events could be simultaneously evaluated histologically. Stromal activation was defined and then evaluated. Survival analysis showed that the stromal activation was correlated with overall survival and disease-free survival (P<0.001 for all). The expression of LOX was significantly increased in the intense activation subgroup (P<0.001).Conclusion: Quantifying assessment of the stroma indicates that the LOX may be a stromal marker for GC and stromal activation, which is not only responsible for the ECM remodeling morphologically, but also for the formation of invasive properties and recurrence. These results support the possibility to integrate morphological and molecular biomarker information for cancer research by the biomedical application of QDs. Keywords: nanomedicine, cancer stromal, gastric cancer, multiplexed molecular imaging Peng CWLiu JYYang GFLi YDove Medical PressarticleQuantum dotsCancer stromalMultiplexed molecular imagingNanomedicineMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 161-174 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Quantum dots Cancer stromal Multiplexed molecular imaging Nanomedicine Medicine (General) R5-920
spellingShingle	Quantum dots Cancer stromal Multiplexed molecular imaging Nanomedicine Medicine (General) R5-920 Peng CW Liu JY Yang GF Li Y Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells
description	Chunwei Peng,1 Jiuyang Liu,1 Guifang Yang,2 Yan Li3 1Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, 2Department of Pathology, Zhongnan Hospital of Wuhan University, Wuchang District, Wuhan, 3Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital Affiliated to the Capital Medical University, Yangfangdian, Beijing, People’s Republic of China Purpose: Semiconductor quantum dots (QDs) are a promising alternative to organic fluorescent dyes for multiplexed molecular imaging of cancer stroma, which have great advantages in holistically analyzing the complex interactions among cancer stromal components in situ.Patients and methods: A QD probe-based multiplexed spectral molecular imaging method was established for simultaneous imaging. Three tissue microarrays (TMAs) including 184 gastric cancer (GC) tissues were constructed for the study. Multispectral analyses were performed for quantifying stromal biomarkers, such as lysyl oxidase (LOX). The stromal status including infiltrating of immune cells (high density of macrophages), angiogenesis (high density of microvessel density [MVD], low neovessel maturation) and extracellular matrix (ECM) remodeling (low density of type IV collagen, intense expression of matrix metalloproteinase 9 [MMP-9]) was evaluated.Results: This study compared the imaging features of the QD probe-based single molecular imaging method, immunohistochemistry, and organic dye-based immunofluorescent methods, and showed the advantages of the QD probe-based multiple molecular imaging method for simultaneously visualizing complex components of cancer stroma. The risk of macrophages in high density, high MVD, low neomicrovessel maturation, MMP-9 expression and low type IV collagen was significantly increased for the expression of LOX. With the advantages of the established QD probe-based multiplexed molecular imaging method, the spatial relationship between LOX and stromal essential events could be simultaneously evaluated histologically. Stromal activation was defined and then evaluated. Survival analysis showed that the stromal activation was correlated with overall survival and disease-free survival (P<0.001 for all). The expression of LOX was significantly increased in the intense activation subgroup (P<0.001).Conclusion: Quantifying assessment of the stroma indicates that the LOX may be a stromal marker for GC and stromal activation, which is not only responsible for the ECM remodeling morphologically, but also for the formation of invasive properties and recurrence. These results support the possibility to integrate morphological and molecular biomarker information for cancer research by the biomedical application of QDs. Keywords: nanomedicine, cancer stromal, gastric cancer, multiplexed molecular imaging
format	article
author	Peng CW Liu JY Yang GF Li Y
author_facet	Peng CW Liu JY Yang GF Li Y
author_sort	Peng CW
title	Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells
title_short	Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells
title_full	Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells
title_fullStr	Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells
title_full_unstemmed	Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells
title_sort	lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/414f7f0c63e744988185ebf33ef8c040
work_keys_str_mv	AT pengcw lysyloxidaseactivatescancerstromalcellsandpromotesgastriccancerprogressionquantumdotbasedidentificationofbiomarkersincancerstromalcells AT liujy lysyloxidaseactivatescancerstromalcellsandpromotesgastriccancerprogressionquantumdotbasedidentificationofbiomarkersincancerstromalcells AT yanggf lysyloxidaseactivatescancerstromalcellsandpromotesgastriccancerprogressionquantumdotbasedidentificationofbiomarkersincancerstromalcells AT liy lysyloxidaseactivatescancerstromalcellsandpromotesgastriccancerprogressionquantumdotbasedidentificationofbiomarkersincancerstromalcells
_version_	1718399452916482048

Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells

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