Research Article

Coevolution of the tumor microenvironment revealed by quantum dot-based multiplexed imaging of hepatocellular carcinoma

Department of Oncology, Zhongnan Hospital of Wuhan University & Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Number 169 Donghu Road, Wuchang District, Wuhan, 430071, PR China

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Chun-Wei Peng

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Jing-Ping Yuan

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Zhi-Ling Zhang

Key Laboratory of Analytical Chemistry for Biology & Medicine (Ministry of Education), College of Chemistry & Molecular Sciences, Research Center for Nanobiology & Nanomedicine (MOE 985 Innovative Platform) & State Key Laboratory of Virology, Wuhan University, Wuhan, 430072, PR China

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Dai-Wen Pang

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Yan Li

* Author for correspondence

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Email the corresponding author at liyansd2@163.com

Published Online:3 Jul 2013https://doi.org/10.2217/fon.13.63

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Abstract

Aim: This study aimed to provide new insights into the mechanisms of hepatocellular carcinoma (HCC) invasion by simultaneously imaging tumor cells and major components of the tumor microenvironment. Materials & methods: Formalin-fixed paraffin-embedded human HCC tissues were studied by conventional immunohistochemistry and quantum dot-based multiplexed imaging to reveal type IV collagen, LOX and tumor angiogenesis. Results: Type IV collagen degradation and repatterning in the extracellular matrix (ECM) was a continuous process, making the ECM harder, although more fragile and less resistant to cancer invasion. The distribution of LOX among cancer nests was heterogeneous, with higher expression in small cancer nests and lower expression in large cancer nests. LOX expression in cancer cells was associated with rigid stroma and tumor angiogenesis. Tumor angiogenesis occurred with type IV collagen presence. At the cancer invasion front, the ECM was hydrolyzed, with the prominent linear reorientation of type IV collagen surrounding cancer nests adjacent to neovessels. Conclusion: The visualization of the temporal–spatial relationship between type IV collagen, LOX and tumor angiogenesis revealed the coevolution process of HCC cells and their microenvironment, emphasizing an active role of the ECM during cancer invasion.

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Vol. 9, No. 7

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Published online 3 July 2013

Published in print July 2013

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Financial & competing interests disclosure

This research was supported by the National Natural Science Foundation of China (grant no. 81230031/H18), National Science and Technology Major Project (grant no. 2012ZX10002012-12) and National University Students Innovation Training Project of China (grant no. 111048673). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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