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Up-regulation of Tropomyosin related kinase B contributes to resistance to detachment-induced apoptosis in hepatoma multicellular aggregations

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Abstract

To elucidate the molecular mechanisms of resistance to detachment-induced apoptosis, we cultured BEL7402 hepatoma cells on plates coated with poly (2-hydroxyethyl methacrylate), which blocked access to the extracellular matrix. When BEL7402 hepatoma cells were suspended, they could self-assemble into aggregations and resist to detachment-induced apoptosis. Expression of TrkB on detached cells was much higher than that of attached ones. Protein structure analysis revealed that TrkB contained adhesion domain, which might contribute to the aggregation formation of hepatoma cells. These aggregations had higher proliferation indices with BDNF treatment. These data demonstrate that TrkB may contribute to metastasis by facilitating formation of multicellular aggregations and induce their resistance to detachment-induced apoptosis.

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Abbreviations

BDNF:

Brain-derived neurotrophic factor

CCK8:

Cell counting kit-8

ECM:

Extra cellular matrix

FCM:

Flow cytometry

HCC:

Hepatocellular carcinoma

LRR:

Leucine rich repeat

Poly-HEMA:

Poly (2-hydroxyethyl methacrylate)

SMART:

Simple Modular Architecture Research Tool

TrkB:

Tropomyosin related kinase B

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Acknowledgements

This work was supported by grant from the Natural Science Foundation of China (No. 30700357) and grant from Natural Science Foundation of Shandong Province (No. Q2006C06).The authors gratefully acknowledge Prof. Youhai Chen (Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA) for helpful discussion about this work.

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Authors and Affiliations

  1. Institute of Immunology, Shandong University School of Medicine, 44, West Wenhua Road, Jinan, 250012, China

    Zhiyong Zhang, Lihui Han, Xiaohong Liang & Wensheng Sun

  2. Department of Pathophysiology, Shandong University School of Medicine, 44, West Wenhua Road, Jinan, 250012, China

    Yugang Liu

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  1. Zhiyong Zhang
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  2. Lihui Han
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  3. Yugang Liu
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  4. Xiaohong Liang
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  5. Wensheng Sun
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Correspondence to Wensheng Sun.

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Zhiyong Zhang and Lihui Han contributed equally to this work.

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Zhang, Z., Han, L., Liu, Y. et al. Up-regulation of Tropomyosin related kinase B contributes to resistance to detachment-induced apoptosis in hepatoma multicellular aggregations. Mol Biol Rep 36, 1211–1216 (2009). https://doi.org/10.1007/s11033-008-9299-z

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