Full text

Turn on search term navigation

© 2013. This work is published under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Endotrophin is a cleavage product of collagenVIα3 (COL6A3). Here, we explore the relationship between thiazolidinediones (TZDs), endotrophin and cisplatin resistance in the context of a mammary tumour model. COL6A3 levels are increased in response to cisplatin exposure in tumours. Endotrophin, in turn, causes cisplatin resistance. The effects of endotrophin can be bypassed, either through use of COL6 null (COL6−/−) mice or by administering TZDs in wild‐type mice (leading to a downregulation of endotrophin). Both approaches sensitize tumours to cisplatin through the suppression of endotrophin‐induced epithelial–mesenchymal transition. The beneficial effects of TZDs on cisplatin sensitivity are diminished in COL6−/− mice, whereas endotrophin+ tumours are sensitive to the TZD/cisplatin combination. Therefore, the chemosensitization obtained with TZDs is achieved through a downregulation of endotrophin. Treatment with an endotrophin neutralizing antibody in combination with cisplatin completely inhibits tumour growth of tumour allografts. Combined, our data suggest that endotrophin levels are a strong prognostic marker for the effectiveness of the combination therapy of TZDs with cisplatin, and neutralization of endotrophin activity dramatically improves the therapeutic response to combination therapy.

Details

Title
Inhibition of endotrophin, a cleavage product of collagen VI, confers cisplatin sensitivity to tumours
Author
Park, Jiyoung 1 ; Morley, Thomas S 1 ; Scherer, Philipp E 2 

 Departments of Internal Medicine, Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA 
 Departments of Internal Medicine, Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Cell Biology, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Simmons Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA 
Pages
935-948
Section
Research Articles
Publication year
2013
Publication date
Jun 2013
Publisher
EMBO Press
ISSN
17574676
e-ISSN
17574684
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2299122420
Copyright
© 2013. This work is published under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.