The Cell Surface Heparan Sulfate Proteoglycan Syndecan-3 Promotes Ovarian Cancer Pathogenesis
Abstract
:1. Introduction
2. Results
2.1. Syndecan-3 Is Overexpressed in Ovarian Cancer
2.2. Syndecan-3 Depletion Affects Colony Formation and 3D Spheroid Growth of Human SKOV3 and CAOV3 Ovarian Cancer Cells
2.3. Impact of Syndecan-3 on the Chemotherapy Response in Ovarian Cancer
2.4. Syndecan-3 Shows Functional Interactions with Stat3 Signaling and Is Associated with Stemness-Associated Signaling Pathways in STRING Analysis
3. Discussion
4. Materials and Methods
4.1. Cell Culture
4.2. siRNA Transfection
4.3. Total RNA Extraction and cDNA Synthesis
4.4. Quantitative Real-Time PCR
4.5. Western Blotting
4.6. Flow Cytometry
4.7. MTT Cell Viability and Chemosensitivity Assay
4.8. Scratch Wound Assay
4.9. Hanging Drop Assay for 3D Sphere Formation
4.10. Cell Colony Formation
4.11. TNM, Kaplan–Meier Plot and STRING Analysis
4.12. Microarray Gene Expression Database of Epithelial Ovarian Cancer Subtype CSIOVDB
4.13. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Cell Line | Drug | IC50 [nM] | Combination Index (CI) [nM] | ||||
---|---|---|---|---|---|---|---|
Control | Sequence 1 | Sequence 2 | Control | Sequence 1 | Sequence 2 | ||
SKOV3 | Taxol | 2.909 | 1.679 | 0.4900 | - | - | - |
Cisplatin | 2.270 | 2.887 | 1.355 | - | - | - | |
Taxol/Cisplatin | - | - | - | 0.930 | 18.198 | <0.001 | |
CAOV3 | Taxol | 1.952 | 1.947 | 1.985 | - | - | - |
Cisplatin | 1.222 | 1.304 | 1.360 | - | - | ||
Taxol/Cisplatin | - | - | - | 13.013 | 10.649 | 12.774 |
mRNA | Sequence (Forward) | Sequence (Reverse) |
---|---|---|
ACTB | TCAAGATCATTGCTCCTCCTGAG | ACATCTGCTGGAAGGTGGACA |
CDH1 | CAAAGCCCAGAATCCCCAAG | CACACCTGGAATTGGGCAAA |
Gli1 | TTCCTACCAGAGTCCCAAGT | CCCTATGTGAAGCCCTATTT |
Gli2 | GTCAGAGCCATCAAGACCGAGA | GCATCTCCACGCCACTGTCATT |
Gli3 | TCAGCAAGTGGCTCCTATGGTC | GCTCTGTTGTCGGCTTAGGATC |
Hes1 | GTGAAGCACCTCCGGAAC | CGTTCATGCACTCGCTGA |
Hey2 | TTGCCCATGCCTAAACTAGTGC | TCTCACGTGCTTGATTTCAGCATA |
Msi1 | AGCTTCCCTCTCCCTCATTCC | GGAATTCCAGGGTCCTGAGC |
Msi2 | CCTAGTATGCTTGCCTCACAAACG | CGTCATCAGGGAGAAGCACAG |
Notch1 | GGTGAGACCTGCCTGAATG | GTTGGGGTCCTGGCATC |
PTCH1 | GGTGGCACAGTCAAGAACA | ACCAAGAGCGAGAAATGG |
Robo1 | GCATCGCTGGAAGTAGCCATACT | CATGAAATGGTGGGCTCAGGAT |
SDC3 | TGCCTCAGAAGAGTATCCTG | CTTGTCAGGCTTCTGGTATG |
SFRP1 | GATGCAGGAGGCTCAGGTGAT | GCTGGCAACAGGTCAGAACG |
SHH | GAAAGCAGAGAACTCGGTGG | GGAAAGTGAGGAAGTCGCTG |
Snail | CGAGCCCAGGCAGCTATTTC | CCCGACAAGTGACAGCCATT |
Src | ACCACCTTTGTGGCCCTCTATG | GCCACCAGTCTCCCTCTGTGTT |
TCF7L1 | AAGGTGCCTGCCACTTCCTC | CCTGCCACTCTGGGATTGTG |
TCF7L2 | AAACCAGCTGCCGCTTTTATG | GCAACATCAACATGCCTAGGTTTT |
Twist | GCGGCCAGGTACATCGACTT | TGCAGCTTGCCATCTTGGAG |
Vimentin | TCAGCATCACGATGACCTTGAA | CTGCAGAAAGGCACTTGAAAGC |
Wnt 3A | AGGTCCCACAGCCCTGAGAT | TCCAGGAAAGCGGACCATTT |
Wnt 5A | TCGTTAGCAGCATCAGTCCACA | GACCTGTGCCTTCGTGCCTA |
ZEB1 | CAGCCCTGCAGTCCAAGAAC | TTGTCTTTCATCCTGATTTCCATTT |
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Hillemeyer, L.; Espinoza-Sanchez, N.A.; Greve, B.; Hassan, N.; Chelariu-Raicu, A.; Kiesel, L.; Götte, M. The Cell Surface Heparan Sulfate Proteoglycan Syndecan-3 Promotes Ovarian Cancer Pathogenesis. Int. J. Mol. Sci. 2022, 23, 5793. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105793
Hillemeyer L, Espinoza-Sanchez NA, Greve B, Hassan N, Chelariu-Raicu A, Kiesel L, Götte M. The Cell Surface Heparan Sulfate Proteoglycan Syndecan-3 Promotes Ovarian Cancer Pathogenesis. International Journal of Molecular Sciences. 2022; 23(10):5793. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105793
Chicago/Turabian StyleHillemeyer, Lara, Nancy Adriana Espinoza-Sanchez, Burkhard Greve, Nourhan Hassan, Anca Chelariu-Raicu, Ludwig Kiesel, and Martin Götte. 2022. "The Cell Surface Heparan Sulfate Proteoglycan Syndecan-3 Promotes Ovarian Cancer Pathogenesis" International Journal of Molecular Sciences 23, no. 10: 5793. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105793