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Research
jingshan tong
UPMC Hillman Cancer Center
Corresponding Author
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Background
Overexpression of P2 × 7R has been observed in several tumors and is related to cancer advancement and metastasis. However, the role of P2 × 7R in colorectal cancer (CRC) patients is not well understood.
Methods
In the current study, overexpression of P2 × 7R and the effects at the molecular and functional levels in CRC were assessed in a mouse orthotopic model. Functional assays, such as the CCK-8 assay, wound healing and transwell assay, were used to determine the biological role of P2 × 7R in CRC cells. CSC-related genes and properties were detected via sphere formation and real-time PCR assays. The underlying mechanisms were explored by Western blotting, real-time PCR and Flow cytometry.
Results
In this study, we found that overexpression of P2 × 7R increase in the in vivo growth of tumors. P2 × 7R overexpression also increased CD31, VEGF and concurrent angiogenesis. P2 × 7R upregulates aldehyde dehydrogenase-1 (ALDH1) and CSC characteristics. Transplanted tumor cells with P2 × 7R overexpression stimulated cytokines to recruit TAMs to increase the growth of tumors. We also found that the NF-κB signaling pathway is involved in P2 × 7R-induced cytokine upregulation.
Conclusion
P2 × 7R promotes NF-κB-dependent cytokine induction, which leads to tumor-associated macrophage (TAM) recruitment to control tumor growth and advancement and remodeling of the stroma. Our findings demonstrate that P2 × 7R plays a key role in TAM recruitment, which may be a therapeutic target for CRC patients.
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Figure 7
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
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.
Research
jingshan tong
UPMC Hillman Cancer Center
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 11 May, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Overexpression of P2 × 7R has been observed in several tumors and is related to cancer advancement and metastasis. However, the role of P2 × 7R in colorectal cancer (CRC) patients is not well understood.
Methods
In the current study, overexpression of P2 × 7R and the effects at the molecular and functional levels in CRC were assessed in a mouse orthotopic model. Functional assays, such as the CCK-8 assay, wound healing and transwell assay, were used to determine the biological role of P2 × 7R in CRC cells. CSC-related genes and properties were detected via sphere formation and real-time PCR assays. The underlying mechanisms were explored by Western blotting, real-time PCR and Flow cytometry.
Results
In this study, we found that overexpression of P2 × 7R increase in the in vivo growth of tumors. P2 × 7R overexpression also increased CD31, VEGF and concurrent angiogenesis. P2 × 7R upregulates aldehyde dehydrogenase-1 (ALDH1) and CSC characteristics. Transplanted tumor cells with P2 × 7R overexpression stimulated cytokines to recruit TAMs to increase the growth of tumors. We also found that the NF-κB signaling pathway is involved in P2 × 7R-induced cytokine upregulation.
Conclusion
P2 × 7R promotes NF-κB-dependent cytokine induction, which leads to tumor-associated macrophage (TAM) recruitment to control tumor growth and advancement and remodeling of the stroma. Our findings demonstrate that P2 × 7R plays a key role in TAM recruitment, which may be a therapeutic target for CRC patients.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
This is a list of supplementary files associated with this preprint. Click to download.
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