LOX-catalyzed collagen stabilization is a proximal cause for intrinsic resistance to chemotherapy
Please always quote using this URN: urn:nbn:de:bvb:20-opus-227008
- The potential of altering the tumor ECM to improve drug response remains fairly unexplored. To identify targets for modification of the ECM aiming to improve drug response and overcome resistance, we analyzed expression data sets from pre-treatment patient cohorts. Cross-evaluation identified a subset of chemoresistant tumors characterized by increased expression of collagens and collagen-stabilizing enzymes. We demonstrate that strong collagen expression and stabilization sets off a vicious circle of self-propagating hypoxia, malignantThe potential of altering the tumor ECM to improve drug response remains fairly unexplored. To identify targets for modification of the ECM aiming to improve drug response and overcome resistance, we analyzed expression data sets from pre-treatment patient cohorts. Cross-evaluation identified a subset of chemoresistant tumors characterized by increased expression of collagens and collagen-stabilizing enzymes. We demonstrate that strong collagen expression and stabilization sets off a vicious circle of self-propagating hypoxia, malignant signaling, and aberrant angiogenesis that can be broken by an appropriate auxiliary intervention: Interfering with collagen stabilization by inhibition of lysyl oxidases significantly enhanced response to chemotherapy in various tumor models, even in metastatic disease. Inhibition of collagen stabilization by itself can reduce or enhance tumor growth depending on the tumor type. The mechanistical basis for this behavior is the dependence of the individual tumor on nutritional supply on one hand and on high tissue stiffness for FAK signaling on the other.…
Author: | Leonie Rossow, Simona Veitl, Sandra Vorlová, Jacqueline K. Wax, Anja E. Kuhn, Verena Maltzahn, Berin Upcin, Franziska Karl, Helene Hoffmann, Sabine Gätzner, Matthias Kallius, Rajender Nandigama, Daniela Scheld, Ster Irmak, Sabine Herterich, Alma Zernecke, Süleyman Ergün, Erik Henke |
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URN: | urn:nbn:de:bvb:20-opus-227008 |
Document Type: | Journal article |
Faculties: | Graduate Schools / Graduate School of Life Sciences |
Medizinische Fakultät / Institut für Anatomie und Zellbiologie | |
Language: | English |
Parent Title (English): | Oncogene |
Year of Completion: | 2018 |
Volume: | 37 |
Pagenumber: | 4921-4940 |
Source: | Oncogene (2018) 37:4921–4940 |
DOI: | https://doi.org/10.1038/s41388-018-0320-2 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | Cancer models; Cancer therapeutic resistance; Targeted therapies; Tumour angiogenesis |
Release Date: | 2022/10/08 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |