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Cited by 56Mesenchymal stem cell researchSarcoma Diagnosis and TreatmentCancer Cells and Metastasis

Adipose-derived mesenchymal stem cells promote osteosarcoma proliferation and metastasis by activating the STAT3 pathway

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Wang, Yan, Chu, Yijing, Yue, Bin, Ma, Xuexiao, Zhang, Guoqing, Xiang, Hongfei, Liu, Yong, Wang, Tianrui +2 more·2017·Oncotarget
DOI 10.18632/oncotarget.15866PMC PMC5410345
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Abstract

// Yan Wang 1, * , Yijing Chu 2, * , Bin Yue 1 , Xuexiao Ma 1 , Guoqing Zhang 1 , Hongfei Xiang 1 , Yong Liu 1 , Tianrui Wang 1 , Xiaolin Wu 1 , Bohua Chen 1 1 Department of Orthopaedic Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China 2 Department of Obstetrics and Gynecology, the Affiliated Hospital of Qingdao University, Qingdao, China * These authors have contributed equally to this work Correspondence to: Bohua Chen, email: bhchen@hotmail.com Keywords: osteosarcoma, adipose-derived mesenchymal stem cells, tumour microenvironment, signal transducer and activator of transcription 3, matrix metalloproteinase Received: July 25, 2016 Accepted: February 06, 2017 Published: March 03, 2017 ABSTRACT Osteosarcoma is the most common primary bone malignancy in children and young adults, but the role of adipose-derived mesenchymal stem cells (ADSCs) in the rapid progression of osteosarcoma is still unclear. Here, we found that ADSCs promoted tumour growth and invasion by increasing matrix metalloproteinase 2/9 (MMP2/9) expression in tumour cells. The persistent activation of signal transducer and activator of transcription 3 (STAT3) has been shown to directly promote tumour growth by mediating a wide spectrum of cellular responses, and STAT3 activation was detected in osteosarcoma cells co-cultured with ADSCs or treated with ADSC-conditioned medium. Furthermore, siRNA-mediated STAT3 inhibition in osteosarcoma cells decreased cell proliferation and invasion and down-regulated MMP2/9 expression. In addition, a nude mouse model of osteosarcoma was established by injecting luciferase-labelled MG63 cells into the tibia. As shown in in vivo bioluminescence images, ADSCs promoted tumour cell proliferation, invasion progression and metastasis. STAT3 inhibition attenuated tumour growth and metastasis and prolonged the survival of these mice. After the siRNA treatment, the MMP2, MMP9 and Ki67 levels decreased. Based on these data, stromal ADSCs promote osteosarcoma progression by increasing STAT3 signalling-mediated MMP2/9 expression.

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  • Adipose tissue-derived mesenchymal stromal cell-mediated activation of the STAT-3 pathway in osteosarcoma increased MMP2/9 and decreased E-cadherin expression, promoting tumour progression.

    “The ADMSCs-mediated activation of the STAT-3 pathway in osteosarcoma increased MMP2/9 and decreased E-cadherin expression, promoting tumour progression [83].”

    From Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice (2019) · cites this paper as [83]

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Cited by

Sorted by citations

Authors
Wang, Y., Chu, Y., Yue, B., Ma, X., Zhang, G., Xiang, H., Liu, Y., Wang, T., Wu, X., & Chen, B.
Affiliations
Affiliated Hospital of Qingdao University (CN)
Corresponding author
  • Wang, Yan
  • Chu, Yijing
ORCID
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2017-03-03
Volume
8
Issue
14
Pages
23803-23816
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.15866
PMC
PMC5410345
OpenAlex
W2592338101
Cited by
56
References
4
Citations by year
2026: 3 · 2025: 5 · 2024: 1 · 2023: 3 · 2022: 8 · 2021: 7 · 2020: 7 · 2019: 12 · 2018: 7 · 2017: 3
FWCI
4.56
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81371998)
  • Qingdao University
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
osteosarcoma, adipose-derived stem cells, STAT3 signaling, MMP2/9, tumor microenvironment, tumor cell proliferation, tumor invasion, metastasis, stromal cells, conditioned medium, STAT3 inhibition
MeSH terms
Adult, Animals, Bone Neoplasms, Humans, Male, Mice, Nude, Neoplasm Metastasis, Osteosarcoma, Signal Transduction, Coculture Techniques, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Cell Proliferation, STAT3 Transcription Factor, Mice, Mesenchymal Stem Cells, Heterografts

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