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Research article
Claire Wells
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1926-6282
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Background Monocytes are a major component of the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC). However, the complex interactions between tumor cells and monocytes and their role in tumor invasion have not been fully established. Methods To specifically test the impact of interaction on invasive potential two PDAC cell lines PaTu8902 and CFPAC-1 were selected on their ability to form invasive adhesions, otherwise known as invadopodia and invade in a spheroid invasion assay. Results Interestingly when the PDAC cells were co-cultured with undifferentiated THP1 monocyte-like cells invadopodia formation was significantly suppressed. Moreover, conditioned media of THP1 cells (CM) was also able to suppress invadopodia formation. Further investigation revealed that both tissue inhibitor of metalloproteinase (TIMP) 1 and 2 were present in the CM. However, suppression of invadopodia formation was found that was specific to TIMP2 activity. Conclusions Our findings indicate that TIMP2 levels in the tumour microenvironment may have prognostic value in patients with PDAC. Furthermore, activation of TIMP2 expressing monocytes in the primary tumour could present a potential therapeutic opportunity to suppress cell invasion in PDAC
Keywords
Pancreatic ductal adenocarcinoma, monocytes, tumor microenvironment, TIMP2, invadopodia
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CURRENT STATUS: Published
View the published article at BMC Cancer.
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Submission checks complete
On 04 Dec, 2019
Editorial decision: Accept
On 03 Dec, 2019
Version 3
Posted 27 Nov, 2019
No comments provided
Editorial decision: Minor revision
On 29 Nov, 2019
Editor assigned
On 27 Nov, 2019
Editor invited
On 26 Nov, 2019
Submission checks complete
On 25 Nov, 2019
No comments provided
Review #1 received
Received 13 Nov, 2019
Editorial decision: Minor revision
On 13 Nov, 2019
Review #2 received
Received 08 Nov, 2019
Editor assigned
On 29 Oct, 2019
Reviewers invited
Invitations sent on 29 Oct, 2019
Reviewer #1 agreed
On 29 Oct, 2019
Reviewer #2 agreed
On 29 Oct, 2019
Submission checks complete
On 28 Oct, 2019
Editor invited
On 28 Oct, 2019
No comments provided
Review #1 received
Received 10 Jul, 2019
Editorial decision: Major revision
On 10 Jul, 2019
Review #2 received
Received 09 Jul, 2019
Reviewer #2 agreed
On 24 Jun, 2019
Reviewers invited
Invitations sent on 21 Jun, 2019
Reviewer #1 agreed
On 21 Jun, 2019
Submission checks complete
On 19 Jun, 2019
Editor invited
On 17 Jun, 2019
Editor assigned
On 17 Jun, 2019
First submitted
On 11 Jun, 2019
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Subject Areas
Cancer Biology
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A new preprint design is coming!
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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
Claire Wells
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1926-6282
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.
No community comments so far
Submission checks complete
On 04 Dec, 2019
Editorial decision: Accept
On 03 Dec, 2019
Version 3
Posted 27 Nov, 2019
No comments provided
Editorial decision: Minor revision
On 29 Nov, 2019
Editor assigned
On 27 Nov, 2019
Editor invited
On 26 Nov, 2019
Submission checks complete
On 25 Nov, 2019
No comments provided
Review #1 received
Received 13 Nov, 2019
Editorial decision: Minor revision
On 13 Nov, 2019
Review #2 received
Received 08 Nov, 2019
Editor assigned
On 29 Oct, 2019
Reviewers invited
Invitations sent on 29 Oct, 2019
Reviewer #1 agreed
On 29 Oct, 2019
Reviewer #2 agreed
On 29 Oct, 2019
Submission checks complete
On 28 Oct, 2019
Editor invited
On 28 Oct, 2019
No comments provided
Review #1 received
Received 10 Jul, 2019
Editorial decision: Major revision
On 10 Jul, 2019
Review #2 received
Received 09 Jul, 2019
Reviewer #2 agreed
On 24 Jun, 2019
Reviewers invited
Invitations sent on 21 Jun, 2019
Reviewer #1 agreed
On 21 Jun, 2019
Submission checks complete
On 19 Jun, 2019
Editor invited
On 17 Jun, 2019
Editor assigned
On 17 Jun, 2019
First submitted
On 11 Jun, 2019
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 Monocytes are a major component of the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC). However, the complex interactions between tumor cells and monocytes and their role in tumor invasion have not been fully established. Methods To specifically test the impact of interaction on invasive potential two PDAC cell lines PaTu8902 and CFPAC-1 were selected on their ability to form invasive adhesions, otherwise known as invadopodia and invade in a spheroid invasion assay. Results Interestingly when the PDAC cells were co-cultured with undifferentiated THP1 monocyte-like cells invadopodia formation was significantly suppressed. Moreover, conditioned media of THP1 cells (CM) was also able to suppress invadopodia formation. Further investigation revealed that both tissue inhibitor of metalloproteinase (TIMP) 1 and 2 were present in the CM. However, suppression of invadopodia formation was found that was specific to TIMP2 activity. Conclusions Our findings indicate that TIMP2 levels in the tumour microenvironment may have prognostic value in patients with PDAC. Furthermore, activation of TIMP2 expressing monocytes in the primary tumour could present a potential therapeutic opportunity to suppress cell invasion in PDAC
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
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