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Cited by 65Cellular Mechanics and InteractionsProtease and Inhibitor Mechanisms3D Printing in Biomedical Research

Study on Invadopodia Formation for Lung Carcinoma Invasion with a Microfluidic 3D Culture Device

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Wang, Shanshan, Li, Encheng, Gao, Yanghui, Wang, Yan, Guo, Zhe, He, Jiarui, Zhang, Jianing, Gao, Zhancheng +1 more·2013·PLoS ONE
DOI 10.1371/journal.pone.0056448PMC PMC3575410
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Abstract

Invadopodia or invasive feet, which are actin-rich membrane protrusions with matrix degradation activity formed by invasive cancer cells, are a key determinant in the malignant invasive progression of tumors and represent an important target for cancer therapies. In this work, we presented a microfluidic 3D culture device with continuous supplement of fresh media via a syringe pump. The device mimicked tumor microenvironment in vivo and could be used to assay invadopodia formation and to study the mechanism of human lung cancer invasion. With this device, we investigated the effects of epidermal growth factor (EGF) and matrix metalloproteinase (MMP) inhibitor, GM6001 on invadopodia formation by human non-small cell lung cancer cell line A549 in 3D matrix model. This device was composed of three units that were capable of achieving the assays on one control group and two experimental groups' cells, which were simultaneously pretreated with EGF or GM6001 in parallel. Immunofluorescence analysis of invadopodia formation and extracellular matrix degradation was conducted using confocal imaging system. We observed that EGF promoted invadopodia formation by A549 cells in 3D matrix and that GM6001 inhibited the process. These results demonstrated that epidermal growth factor receptor (EGFR) signaling played a significant role in invadopodia formation and related ECM degradation activity. Meanwhile, it was suggested that MMP inhibitor (GM6001) might be a powerful therapeutic agent targeting invadopodia formation in tumor invasion. This work clearly demonstrated that the microfluidic-based 3D culture device provided an applicable platform for elucidating the mechanism of cancer invasion and could be used in testing other anti-invasion agents.

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Cited by

Sorted by citations

Authors
Wang, S., Li, E., Gao, Y., Wang, Y., Guo, Z., He, J., Zhang, J., Gao, Z., & Wang, Q.
Affiliations
  • Dalian Medical University (CN)
  • Peking University People's Hospital (CN)
Corresponding author
  • Gao, Zhancheng
  • Wang, Qi
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-02-18
Volume
8
Issue
2
Pages
e56448
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0056448
PMC
PMC3575410
OpenAlex
W1969160840
Cited by
65
References
3
Citations by year
2026: 1 · 2025: 5 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 8 · 2019: 8 · 2018: 8 · 2017: 6 · 2016: 4 · 2015: 5 · 2014: 8
FWCI
3.29
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (973 Program, 81071228, 2012CB822103, #91129733)
  • National Key Research and Development Program of China (2012CB822103)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Keywords
invadopodia, non-small cell lung cancer, A549 cells, extracellular matrix degradation, epidermal growth factor, epidermal growth factor receptor signaling, matrix metalloproteinase inhibitors, GM6001, tumor microenvironment
MeSH terms
Carcinoma, Carcinoma, Non-Small-Cell Lung, Cell Survival, Dipeptides, Epidermal Growth Factor, Extracellular Matrix, Humans, Lung Neoplasms, Tumor Cells, Cultured, Apoptosis, Cell Line, Tumor, Microfluidic Analytical Techniques

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