Proteomic analysis of lung metastases in a murine breast cancer model reveals divergent influence of CTSB and CTSL overexpression
Abstract: Studies in the MMTV-PyMT (PyMT) breast cancer mouse model have shown a strong influence of the lysosomal cysteine cathepsins B or L on lung metastasis formation. Transgenic expression of human CTSB (tgCTSB) or CTSL (tgCTSL) both led to similar metastatic phenotypes with increased metastatic burden in the PyMT mice. However, recent studies in other tumor models proved marked differences in effects of either cathepsin on the proteome composition. We sought to analyze and compare proteome changes in the metastatic proteome of PyMT mice expressing either tgCTSB or tgCTSL to evaluate similarities and differences in those models.
Performing an explorative, quantitative proteome comparison based on LC-MS/MS, we identified up to 3,000 proteins from murine lung metastases in three independent biological replicates per genotype. In both cases, when compared to wild-type (WT) mice, we noticed a pronounced impact of transgene cathepsin expression on the metastasis proteome. Highlights include increased moesin, integrin beta 1 and vinexin levels in the tgCTSB dataset and increased saposin and granulin levels in the tgCTSL dataset. Importantly, non-supervised hierarchical clustering clearly separated tgCTSB vs. tgCTSL induced proteome changes.
In summary, tgCTSB and tgCTSL both display a strong and distinct impact on proteome composition of lung macrometastases in the PyMT model. Our observations suggest that they impact malignant behavior in distinct ways, thus further emphasizing interest into their tumor-contextual functionality
- Location
-
Deutsche Nationalbibliothek Frankfurt am Main
- Extent
-
Online-Ressource
- Language
-
Englisch
- Notes
-
Journal of cancer. Vol. 8, Issue 19 (2017), 4065-4074, DOI 10.7150/jca.21401, issn: 1837-9664
IN COPYRIGHT http://rightsstatements.org/page/InC/1.0 rs
- Keyword
-
Brustkrebs
Lungenmetastase
Krebs
Onkologie
- Event
-
Veröffentlichung
- (where)
-
Freiburg
- (who)
-
Universität
- (when)
-
2017
- Contributor
-
Albert-Ludwigs-Universität Freiburg. Institut für Molekulare Medizin und Zellforschung
Spemann Graduate School of Biology and Medicine
Albert-Ludwigs-Universität Freiburg. Centre for Biological Signalling Studies
Albert-Ludwigs-Universität Freiburg. Medizinische Fakultät
Albert-Ludwigs-Universität Freiburg. Fakultät für Biologie
Albert-Ludwigs-Universität Freiburg
- DOI
-
10.7150/jca.21401
- URN
-
urn:nbn:de:bsz:25-freidok-136560
- Rights
-
Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
-
25.03.2025, 1:56 PM CET
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Sigloch, Florian Christoph
- Tholen, Martina
- Gómez Aulí, Alejandro
- Biniossek, Martin Lothar
- Reinheckel, Thomas
- Schilling, Oliver
- Albert-Ludwigs-Universität Freiburg. Institut für Molekulare Medizin und Zellforschung
- Spemann Graduate School of Biology and Medicine
- Albert-Ludwigs-Universität Freiburg. Centre for Biological Signalling Studies
- Albert-Ludwigs-Universität Freiburg. Medizinische Fakultät
- Albert-Ludwigs-Universität Freiburg. Fakultät für Biologie
- Albert-Ludwigs-Universität Freiburg
- Universität
Time of origin
- 2017