Abstract
Background
The platelet derived growth factor-D (PDGF-D) plays an important role in breast tumor
aggressiveness. However, limited study has investigated the effect of silencing PDGF-D
on the biological function of breast cancer. The purpose of this study is to clarify
the potential value of PDGF-D as a target for breast cancer treatment.
Methods
Reverse transcription-polymerase chain reaction and western blot were used to detect
PDGF-D expression in 5 different breast cancer cells. The lentiviral vector was usd
to silence PDGF-D in MDA-MB-231 cells. Then, Methyl Thiazolyl Tetrazolium was used
to detect cell viability, 5-Ethynyl-2’- deoxyuridine and a soft agar assay were used
to detect cell proliferation and clonality. Additionally, cell apoptosis after PDGF-D
knockdown was measured by Annexin V/ Prodium Iodide staining, and cell migration was
detected by trans-well assay. Survival rate and tumor size were measured by nude mice
transplantation.
Results
The MDA-MB-231 and SK-BR-3 cell lines showed higher PDGF-D expression than the MCF7
cell lines (P<.05). After the PDGF-D gene was silenced, the growth and colony forming abilitys
ignificantly decreased (P<.05) together with the induction of apoptosis in MDA-MB-231 cells (P<.05). Moreover, MDA-MB-231 cells with PDGF-D silencing showed significantly diminished
aggressive migration and invasion potential compared to other cells (P<.05). In vivo experiments also indicated that PDGF-D silencing inhibited tumor growth
and improved the survival rate of tumor-bearing mice.
Conclusion
Downregulation of PDGF-D had dramatic effects on breast cancer cell proliferation,
apoptosis and migration, which indicates that it plays an important role in breast
cancer development and progression.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical Breast CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Breast cancer challenges and screening in china: lessons from current registry data and population screening studies.Oncologist. 2015; 20: 773-779
- Liver-directed therapies in metastatic colorectal cancer.J Gastrointest Oncol. 2014; 5: 374-387
- Breast cancer: current molecular therapeutic targets and new players.Anticancer Agents Med Chem. 2017; 17: 152-163
- Molecular mechanisms and emerging therapeutic targets of triple-negative breast cancer metastasis.Front Oncol. 2018; 8: 31
- PDGF family function and prognostic value in tumor biology.Biochem Biophys Res Commun. 2018; 503: 984-990
- Effect of PDGF-B aptamer on PDGFRβ/PDGF-B interaction: Molecular dynamics study.J Mol Graph Model. 2018; 82: 145-156
- Platelet-derived growth factor-D promotes colorectal cancer cell migration, invasion and proliferation by regulating Notch1 and matrix metalloproteinase-9.Oncol Lett. 2018; 15: 1573-1579
- Overexpression of platelet-derived growth factor receptor alpha promotes tumor progression and indicates poor prognosis in hepatocellular carcinoma.Oncotarget. 2014; 5: 10307-10317
- PDGF receptors in tumor stroma: Biological effects and associations with prognosis and response to treatment.Adv Drug Deliv Rev. 2017; 121: 117-123
- Epithelial-mesenchymal transition in breast cancer lines is mediated through PDGF-D released by tissue-resident stem cells.Int J Cancer. 2012; 131: 1023-1031
- Over-expression of platelet-derived growth factor-D promotes tumor growth and invasion in endometrial cancer.Int J Mol Sci. 2014; 15: 4780-4794
- C-reactive protein can upregulate VEGF expression to promote ADSC-induced angiogenesis by activating HIF-1α via CD64/PI3k/Akt and MAPK/ERK signaling pathways.Stem Cell Res Ther. 2016; 7: 114
- Platelet-derived growth factor (PDGF) signalling in cancer: rapidly emerging signalling landscape.Cell Biochem Funct. 2015; 33: 257-265
- Clinical significance of platelet derived growth factor-C and -D in gastric cancer.Oncol Lett. 2015; 10: 3495-3501
- The interaction between androgen receptor and PDGF-D in the radiation response of prostate carcinoma.Prostate. 2016; 76: 534-542
- The clinical significance of platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) in gastric cancer: A systematic review and meta-analysis.Crit Rev Oncol Hematol. 2018; 127: 15-28
- Platelet-derived growth factor-D enables liver myofibroblasts to promote tumor lymphangiogenesis in cholangiocarcinoma.J Hepatol. 2019; 70: 700-709
- Specific targeting of PDGFRβ in the stroma inhibits growth and angiogenesis in tumors with high PDGF-BB expression.Theranostics. 2020; 10: 1122-1135
- The PDGF pathway in breast cancer is linked to tumor aggressiveness, triple-negative subtype and early recurrence.Breast Cancer Res Treat. 2018; 169: 231-241
- PDGF-C and PDGF-D signaling in vascular diseases and animal models.Mol Aspects Med. 2018; 62: 1-11
- Platelet-derived growth factor-C and -D in the cardiovascular system and diseases.Mol Aspects Med. 2018; 62: 12-21
- Differential prognostic impact of platelet-derived growth factor receptor expression in NSCLC.Sci Rep. 2019; 9: 10163
- VMP1 related autophagy and apoptosis in colorectal cancer cells: VMP1 regulates cell death.Biochem Biophys Res Commun. 2014; 443: 1041-1047
- Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling.Nat Med. 2018; 24: 463-473
- Afadin cooperates with Claudin-2 to promote breast cancer metastasis.Genes Dev. 2019; 33: 180-193
- Epithelial mesenchymal transition in embryonic development, tissue repair and cancer: a comprehensive overview.J Clin Med. 2017; 7
- An Atypical System for studying epithelial-mesenchymal transition in hepatocellular carcinoma.Sci Rep. 2016; 6: 26282
Article info
Publication history
Published online: June 19, 2021
Accepted:
June 4,
2021
Received in revised form:
May 6,
2021
Received:
September 30,
2020
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
