TY  - JOUR
A1  - Rossow, Leonie
A1  - Veitl, Simona
A1  - Vorlová, Sandra
A1  - Wax, Jacqueline K.
A1  - Kuhn, Anja E.
A1  - Maltzahn, Verena
A1  - Upcin, Berin
A1  - Karl, Franziska
A1  - Hoffmann, Helene
A1  - Gätzner, Sabine
A1  - Kallius, Matthias
A1  - Nandigama, Rajender
A1  - Scheld, Daniela
A1  - Irmak, Ster
A1  - Herterich, Sabine
A1  - Zernecke, Alma
A1  - Ergün, Süleyman
A1  - Henke, Erik
T1  - LOX-catalyzed collagen stabilization is a proximal cause for intrinsic resistance to chemotherapy
JF  - Oncogene
N2  - 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.
KW  - Cancer models
KW  - Cancer therapeutic resistance
KW  - Targeted therapies
KW  - Tumour angiogenesis
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227008
VL  - 37
ER  -