Research Paper Volume 7, Issue 10 pp 816—838

Proteomic identification of prognostic tumour biomarkers, using chemotherapy-induced cancer-associated fibroblasts

Maria Peiris-Pagès 1, 2, , Duncan L. Smith 3, , Balázs Győrffy 4, 5, , Federica Sotgia 1, 2, , Michael P. Lisanti 1, 2, ,

  • 1 The Breast Cancer Now Research Unit, Institute of Cancer Sciences, University of Manchester, UK
  • 2 The Manchester Centre for Cellular Metabolism (MCCM), Institute of Cancer Sciences, University of Manchester, UK
  • 3 The Cancer Research UK Manchester Institute, University of Manchester, UK
  • 4 MTA TTK Lendület Cancer Biomarker Research Group, Budapest, Hungary
  • 5 Semmelweis University 2nd Dept. of Pediatrics, Budapest, Hungary

received: August 13, 2015 ; accepted: September 12, 2015 ; published: October 23, 2015 ;

https://doi.org/10.18632/aging.100808
How to Cite

Abstract

Cancer cells grow in highly complex stromal microenvironments, which through metabolic remodelling, catabolism, autophagy and inflammation nurture them and are able to facilitate metastasis and resistance to therapy. However, these changes in the metabolic profile of stromal cancer-associated fibroblasts and their impact on cancer initiation, progression and metastasis are not well-known. This is the first study to provide a comprehensive proteomic portrait of the azathioprine and taxol-induced catabolic state on human stromal fibroblasts, which comprises changes in the expression of metabolic enzymes, myofibroblastic differentiation markers, antioxidants, proteins involved in autophagy, senescence, vesicle trafficking and protein degradation, and inducers of inflammation. Interestingly, many of these features are major contributors to the aging process. A catabolic stroma signature, generated with proteins found differentially up-regulated in taxol-treated fibroblasts, strikingly correlates with recurrence, metastasis and poor patient survival in several solid malignancies. We therefore suggest the inhibition of the catabolic state in healthy cells as a novel approach to improve current chemotherapy efficacies and possibly avoid future carcinogenic processes.

Abbreviations

AZA: azathioprine; TAX: taxol; CAF: cancer-associated fibroblast; MCT4: monocarboxylate transporter 4; IL6: interleukin 6; ROS: reactive oxygen species; αSMA: α-smooth muscle actin.