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Research article
Xianglan Zhang
Yonsei University
Corresponding Author
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Background : In bone-invasive oral squamous cell carcinoma (OSCC), cancer-associated fibroblasts (CAFs) infiltrate into bony tissue ahead of OSCC cells. In the present study, we aimed to investigate the role of the Axin2-Snail axis in the biological behaviour of CAFs and bone invasion in OSCC.
Methods : The clinicopathological significance of Axin2 and Snail expression was investigated by immunohistochemistry in an OSCC cohort containing 217 tissue samples from patients with long-term follow-up. The influence of the Axin2-Snail axis on the biological behaviour of OSCC cells and CAFs was further investigated both in vitro and in vivo .
Results : Axin2 expression was significantly associated with Snail expression, the desmoplasia status, and bone invasion in patients with OSCC. In multivariate analysis, lymph node metastasis, desmoplasia, Axin2 expression, and Snail expression were independent poor prognostic factors in our cohort. Consistent with these findings, OSCC cells demonstrated attenuated oncogenic activity as well as decreased expression of Snail and various cytokines after Axin2 knockdown in vitro . Among the related cytokines, C-C motif chemokine ligand 5 (CCL5) and interleukin 8 (IL8) demonstrated a strong influence on the biological behaviour of CAFs in vitro . Moreover, both the desmoplastic reaction and osteolytic lesions in the calvaria were predominantly decreased after Axin2 knockdown in OSCC cells in vivo using a BALB/c athymic nude mouse xenograft model.
Conclusions : Oncogenic activities of the Axin2-Snail axis are not limited to the cancer cells themselves but rather extend to CAFs via regulation of the cytokine-mediated cancer-stromal interaction, with further implications for bone invasion as well as a poor prognosis in OSCC.
Keywords
Axin2, Snail, Cytokine, Cancer-stroma crosstalk, CAFs, Bone invasion, Prognosis, OSCC
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View the published article at BMC Cancer.
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On 03 Oct, 2020
Editorial decision: Accept
On 02 Oct, 2020
No comments provided
Editor assigned
On 25 Sep, 2020
Submission checks complete
On 24 Sep, 2020
Editor invited
On 24 Sep, 2020
No comments provided
Review #2 received
Received 13 Sep, 2020
Editorial decision: Minor revision
On 13 Sep, 2020
Reviewer #2 agreed
On 16 Aug, 2020
Review #1 received
Received 14 Jul, 2020
Reviewer #1 agreed
On 22 Jun, 2020
Reviewers invited
Invitations sent on 06 Jun, 2020
Editor assigned
On 25 May, 2020
Submission checks complete
On 24 May, 2020
Editor invited
On 24 May, 2020
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Subject Areas
Cancer Biology
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
See the published version of this preprint at BMC Cancer.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Xianglan Zhang
Yonsei University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Cancer.
Version 3
Posted 13 Oct, 2020
No community comments so far
Submission checks complete
On 03 Oct, 2020
Editorial decision: Accept
On 02 Oct, 2020
No comments provided
Editor assigned
On 25 Sep, 2020
Submission checks complete
On 24 Sep, 2020
Editor invited
On 24 Sep, 2020
No comments provided
Review #2 received
Received 13 Sep, 2020
Editorial decision: Minor revision
On 13 Sep, 2020
Reviewer #2 agreed
On 16 Aug, 2020
Review #1 received
Received 14 Jul, 2020
Reviewer #1 agreed
On 22 Jun, 2020
Reviewers invited
Invitations sent on 06 Jun, 2020
Editor assigned
On 25 May, 2020
Submission checks complete
On 24 May, 2020
Editor invited
On 24 May, 2020
First submitted
On 22 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cancer Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Cancer.
Background : In bone-invasive oral squamous cell carcinoma (OSCC), cancer-associated fibroblasts (CAFs) infiltrate into bony tissue ahead of OSCC cells. In the present study, we aimed to investigate the role of the Axin2-Snail axis in the biological behaviour of CAFs and bone invasion in OSCC.
Methods : The clinicopathological significance of Axin2 and Snail expression was investigated by immunohistochemistry in an OSCC cohort containing 217 tissue samples from patients with long-term follow-up. The influence of the Axin2-Snail axis on the biological behaviour of OSCC cells and CAFs was further investigated both in vitro and in vivo .
Results : Axin2 expression was significantly associated with Snail expression, the desmoplasia status, and bone invasion in patients with OSCC. In multivariate analysis, lymph node metastasis, desmoplasia, Axin2 expression, and Snail expression were independent poor prognostic factors in our cohort. Consistent with these findings, OSCC cells demonstrated attenuated oncogenic activity as well as decreased expression of Snail and various cytokines after Axin2 knockdown in vitro . Among the related cytokines, C-C motif chemokine ligand 5 (CCL5) and interleukin 8 (IL8) demonstrated a strong influence on the biological behaviour of CAFs in vitro . Moreover, both the desmoplastic reaction and osteolytic lesions in the calvaria were predominantly decreased after Axin2 knockdown in OSCC cells in vivo using a BALB/c athymic nude mouse xenograft model.
Conclusions : Oncogenic activities of the Axin2-Snail axis are not limited to the cancer cells themselves but rather extend to CAFs via regulation of the cytokine-mediated cancer-stromal interaction, with further implications for bone invasion as well as a poor prognosis in OSCC.
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
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