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.
Article
Liang Liu
Fudan University Shanghai Cancer Centre
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8003-0503
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The pro-tumor mechanisms of platelets in pancreatic ductal adenocarcinoma (PDAC) are poorly understood. We showed that the count of the CD41+/CD62P + platelets subtype was significantly elevated in stage III/IV patients. An increased level of CD41+/CD62P + platelets could serve as an independent risk factor for stage I/II patients after surgery. Furthermore, we found significantly higher PX1 expression in CD41+/CD62P + platelets than in CD41+/CD62P- platelets in PDAC patients. Mechanistically, PX1 was able to enhance IL-1β secretion in platelets via phosphorylating p38 MAPK and consequently promoted PDAC invasion and metastasis. Finally, we constructed a novel compound named PC63435 by the ligation of carbenoxolone (PX1 inhibitor) and PSGL-1 (CD62P ligand). PC63435 specifically bound to CD41+/CD62P + platelets and blocked the PX1/IL-1β pathway, which suppressed PDAC tumor invasion and metastasis. Our findings revealed that the activation of PX1 in CD41+/CD62P + platelets enhanced PDAC cell malignancy and that may be a potent target for PDAC therapy.
Keywords
Activated platelet, PX1, Platelet-derived IL-1β, PDAC, Malignant potential
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
There is NO Competing Interest.
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementarymaterialsandSupplementaryfigureandtable.pdf
Supplementary materials and figures and tables
Loading...
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 16 Mar, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
This is a preprint. It has not completed peer review.
Article
Liang Liu
Fudan University Shanghai Cancer Centre
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8003-0503
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 16 Mar, 2021
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
The pro-tumor mechanisms of platelets in pancreatic ductal adenocarcinoma (PDAC) are poorly understood. We showed that the count of the CD41+/CD62P + platelets subtype was significantly elevated in stage III/IV patients. An increased level of CD41+/CD62P + platelets could serve as an independent risk factor for stage I/II patients after surgery. Furthermore, we found significantly higher PX1 expression in CD41+/CD62P + platelets than in CD41+/CD62P- platelets in PDAC patients. Mechanistically, PX1 was able to enhance IL-1β secretion in platelets via phosphorylating p38 MAPK and consequently promoted PDAC invasion and metastasis. Finally, we constructed a novel compound named PC63435 by the ligation of carbenoxolone (PX1 inhibitor) and PSGL-1 (CD62P ligand). PC63435 specifically bound to CD41+/CD62P + platelets and blocked the PX1/IL-1β pathway, which suppressed PDAC tumor invasion and metastasis. Our findings revealed that the activation of PX1 in CD41+/CD62P + platelets enhanced PDAC cell malignancy and that may be a potent target for PDAC therapy.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Loading...