LOX-catalyzed collagen stabilization is a proximal cause for intrinsic resistance to chemotherapy
Rossow L, Veitl S, Vorlova S, Wax JK, Kuhn AE, Maltzahn V, Upcin B, Karl F, Hoffmann H, Gaetzner S, Kallius M, Nandigama R, Scheld D, Irmak S, Herterich S, Zernecke A, Ergun S, Henke E (2018)
Publication Type: Journal article
Publication year: 2018
Journal
Book Volume: 37
Pages Range: 4921-4940
Journal Issue: 36
DOI: 10.1038/s41388-018-0320-2
Abstract
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, 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.
Involved external institutions
Julius-Maximilians-Universität Würzburg
Germany (DE)
Universitätsklinikum Würzburg
Germany (DE)
Istanbul Bilgi University / İstanbul Bilgi Üniversitesi
Turkey (TR)
Germany (DE)
Universitätsklinikum Würzburg
Germany (DE)
Istanbul Bilgi University / İstanbul Bilgi Üniversitesi
Turkey (TR)
How to cite
APA:
Rossow, L., Veitl, S., Vorlova, S., Wax, J.K., Kuhn, A.E., Maltzahn, V.,... Henke, E. (2018). LOX-catalyzed collagen stabilization is a proximal cause for intrinsic resistance to chemotherapy. Oncogene, 37(36), 4921-4940. https://doi.org/10.1038/s41388-018-0320-2
MLA:
Rossow, Leonie, et al. "LOX-catalyzed collagen stabilization is a proximal cause for intrinsic resistance to chemotherapy." Oncogene 37.36 (2018): 4921-4940.
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