Investigating the Role of Heparanase in Breast Cancer Development Utilising the MMTV-PyMT Murine Model of Mammary Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Generation of MMTV-PyMTxHPSE−/− Mice
2.2. Genotyping Strategy
2.3. HPSE Enzymatic Activity Assay
2.4. Measurement of HPSE Activity of Mouse Splenic Lysate
2.5. Purification of Human HPSE
2.6. Validation of Purified HPSE by Western Blot
2.7. Mammary Tumour Measurements
2.8. Dissection of Mammary Glands and Mammary Tumours
2.9. Whole Mounting of Mouse Mammary Glands
2.10. H&E Staining
2.11. Immunohistochemistry (IHC)
2.12. Pathological Grading of MMTV-PyMT and MMTV-PyMTxHPSE−/− Mammary Tumour Development
2.13. Microvessel Density Quantification following Anti-CD31 IHC
2.14. H-Scoring of Mammary Tumours
2.15. Extraction of Total Lung RNA and Relative Tumour Burden (RTB) Determination by qPCR
3. Results
3.1. Characterisation of HPSE Expression and Activity Status of MMTV-PyMT and MMTV-PyMTxHPSE−/− Mice
3.2. Evaluation of Spontaneous Mammary Tumour Growth between MMTV-PyMT and MMTV-PyMTxHPSE−/− Mice
3.3. HPSE Expression over Time in MMTV-PyMT Mammary Glands
3.4. The Effect of HPSE on Early- and Late-Stage Tumour Angiogenesis in MMTV-PyMT Mice
3.5. The Role of Host HPSE in Influencing Lung Metastasis of MMTV-PyMT Mammary Tumours
3.6. Evaluation of the Role of HPSE in the Early Stages of Mammary Tumour Development in the MMTV-PyMT Mouse Model
3.7. Investigating the Presence of a Compensatory Mechanism of MMP-2 Expression in MMTV-PyMTxHPSE−/− Mouse Mammary Tumour Lesions
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Primer | Sequence (5′ to 3′) | Size (bp) |
---|---|---|
MMTV-PyMT (F) | AGG AAC CGG CTT CCA GGT AAG A | |
MMTV-PyMT (R) | TTG GTG TTC CAA ACC ATT GCA T | 260 |
HPSE+/+ (F) | GAA GAA CCA TTA TTC ATC TTG CT | |
HPSE+/+ (R) | CCA AGT GCC AGT CTG CAA GT | 143 |
HPSE−/− (F) | GGG ATG GAT GCA GGT CTT C | |
HPSE−/− (R) | CAG ATG GGT GCA GAT TAG ATA T | 300 |
Fabpi (F) | TGG ACA GGA CTG GAC CTC TGC TTT CCT AGA | |
Fabpi (R) | TAG AGC TTT CGG ACA TCA CAG GTC ATT CAG | 200 |
Target | Primary Antibody | Secondary Antibody |
---|---|---|
HPSE | Rabbit polyclonal anti-HPSE (10 μg/mL, B85543, Abcam) | Biotinylated goat anti-rabbit IgG (H+L) (6 μg/mL, BA-1000, Vector Laboratories) |
CD31 | Rabbit polyclonal anti-CD31 (16 μg/mL, AB28364, Abcam) | Biotinylated goat anti-rabbit IgG (H+L) (6 μg/mL, BA-1000, Vector Laboratories) |
Ki67 | Rabbit polyclonal anti-Ki67 (1 μg/mL, AB15580, Abcam) | Biotinylated goat anti-rabbit IgG (H+L) (6 μg/mL, BA-1000, Vector Laboratories) |
Smooth muscle myosin heavy chain (SMMHC) | Rabbit monoclonal anti-SMMHC (clone EPR5335, 1.2 μg/mL, AB124679, Abcam) | Biotinylated goat anti-rabbit IgG (H+L) (6 μg/mL, BA-1000, Vector Laboratories) |
MMP-2 | Rabbit polyclonal anti-MMP-2 (2 μg/mL, AB37150, Abcam) | Biotinylated goat anti-rabbit IgG (H+L) (6 μg/mL, BA-1000, Vector Laboratories) |
Normal rabbit IgG (isotype control) | IgG from rabbit serum (various working concentrations, 18140, Sigma-Aldrich) | Biotinylated goat anti-rabbit IgG (H+L) (6 μg/mL, BA-1000, Vector Laboratories) |
Primer | Sequence 5′ to 3′ |
---|---|
PyMT cDNA (F) | CCA ACA GAT ACA CCC GCA CAT |
PyMT cDNA (R) | GGT CTT GGT CGC TTT CTG GAT A |
Control 18S cDNA (F) | GTA ACC CGT TGA ACC CCA TT |
Control 18S cDNA (R) | CCA TCC AAT CGG TAG TAG CG |
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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Jayatilleke, K.M.; Duivenvoorden, H.M.; Ryan, G.F.; Parker, B.S.; Hulett, M.D. Investigating the Role of Heparanase in Breast Cancer Development Utilising the MMTV-PyMT Murine Model of Mammary Carcinoma. Cancers 2023, 15, 3062. https://doi.org/10.3390/cancers15113062
Jayatilleke KM, Duivenvoorden HM, Ryan GF, Parker BS, Hulett MD. Investigating the Role of Heparanase in Breast Cancer Development Utilising the MMTV-PyMT Murine Model of Mammary Carcinoma. Cancers. 2023; 15(11):3062. https://doi.org/10.3390/cancers15113062
Chicago/Turabian StyleJayatilleke, Krishnath M., Hendrika M. Duivenvoorden, Gemma F. Ryan, Belinda S. Parker, and Mark D. Hulett. 2023. "Investigating the Role of Heparanase in Breast Cancer Development Utilising the MMTV-PyMT Murine Model of Mammary Carcinoma" Cancers 15, no. 11: 3062. https://doi.org/10.3390/cancers15113062