NDLI: Targeting PDGF-CC as a promising therapeutic strategy to inhibit cholangiocarcinoma progression

Content Provider	Springer Nature : BioMed Central
Author	Luo, Zhenchao Zhou, Fangfang Tan, Canliang Yin, Liangchun Bao, Man He, Xiang Li, Haohui Yan, Jian
Abstract	Background Cholangiocarcinoma (CCA) is an aggressive malignancy with limited treatment options and poor prognosis. Platelet-Derived Growth Factor CC (PDGF-CC) has been implicated in the progression of various tumors, but its specific role in CCA is not well understood. This study aims to investigate the expression and function of PDGF-CC in CCA and evaluate its potential as a therapeutic target. Methods We conducted gene expression analysis using the GEPIA database to compare PDGF-CC mRNA levels in CCA tissues and normal tissues. Serum samples from CCA patients were analyzed for PDGF-CC protein levels, and immunohistochemistry was used to assess PDGF-CC expression in tissue samples. The impact of PDGF-CC on CCA cell behavior was examined by knocking out PDGF-CC in HuCCT1 and QBC939 cell lines, followed by assessments of cell proliferation, migration, invasion, and colony formation in vitro. Additionally, the effects of PDGF-CC knockout were evaluated in xenograft models. The therapeutic potential of PDGF-CC inhibition was further explored using pharmacological inhibitors and antibodies. Results PDGF-CC mRNA and protein levels were significantly elevated in CCA tissues and patient sera compared to normal controls. Immunohistochemical analysis confirmed increased PDGF-CC expression in CCA tissues. High PDGF-CC expression correlated with poor overall survival in CCA patients, as shown by Kaplan-Meier analysis. Functional assays revealed that PDGF-CC knockout significantly reduced proliferation, migration, invasion, and colony formation in HuCCT1 and QBC939 cells, the lines with the highest PDGF-CC levels. In vivo, PDGF-CC knockout markedly decreased tumor growth in xenograft models. Pharmacological inhibition of PDGF-CC mirrored the effects of genetic knockout, suggesting it as a viable therapeutic strategy. Conclusions This study underscores the critical role of PDGF-CC in CCA progression and supports the potential of PDGF-CC inhibitors as a therapeutic approach. Given the association between high PDGF-CC expression and poor prognosis, targeting PDGF-CC may improve outcomes for CCA patients. Further clinical investigations are warranted to develop PDGF-CC-targeted therapies for CCA.
Related Links	https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-024-05857-6.pdf
Ending Page	16
Page Count	16
Starting Page	1
File Format	HTM / HTML
ISSN	14795876
DOI	10.1186/s12967-024-05857-6
Journal	Journal of Translational Medicine
Issue Number	1
Volume Number	22
Language	English
Publisher	BioMed Central
Publisher Date	2024-11-14
Access Restriction	Open
Subject Keyword	Biomedicine Medicine Public Health PDGF-CC Cholangiocarcinoma Therapeutic target Xenograft model Cell proliferation Migration Invasion PDGFR inhibitor Ki67 Tumor growth Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Biochemistry, Genetics and Molecular Biology Medicine
Journal Impact Factor	6.1/2023
5-Year Journal Impact Factor	6.3/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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