pr500727h_si_001.xlsx (9.12 kB)
Proteome Profiling of Breast Cancer Biopsies Reveals a Wound Healing Signature of Cancer-Associated Fibroblasts
dataset
posted on 2014-11-07, 00:00 authored by Michael Groessl, Astrid Slany, Andrea Bileck, Kerstin Gloessmann, Dominique Kreutz, Walter Jaeger, Georg Pfeiler, Christopher GernerBreast
cancer is still the most common type of cancer in women;
an important role in carcinogenesis is actually attributed to cancer-associated
fibroblasts. In this study, we investigated whether it is possible
to assess the functional state of cancer-associated fibroblasts through
tumor tissue proteome profiling. Tissue proteomics was performed on
tumor-central, tumor-near, and tumor-distant biopsy sections from
breast adenocarcinoma patients, which allowed us to identify 2074
proteins. Data were interpreted referring to reference proteome profiles
generated from primary human mammary fibroblasts comprising 4095 proteins.
These cells were analyzed in quiescent cell state as well as after
in vitro treatment with TGFβ or IL-1β, stimulating wound
healing or inflammatory processes, respectively. Representative for
cancer cells, we investigated the mammary carcinoma cell line ZR-75-1,
identifying 5212 proteins. All mass analysis data have been made fully
accessible via ProteomeXchange, DOI PXD001311 and PXD001323-8. Comparison
of tissue proteomics data with all of those reference profiles revealed
predominance of cancer cell-derived proteins within the tumor and
fibroblast-derived proteins in the tumor-distant tissue sections.
Remarkably, proteins characteristic for acute inflammation were hardly
identified in the tissue samples. In contrast, several proteins found
by us to be induced by TGFβ in mammary fibroblasts, including
fibulin-5, SLC2A1, and MUC18, were positively identified in all tissue
samples, with relatively higher abundance in tumor neighboring tissue
sections. These findings indicate a predominance of cancer-associated
fibroblasts with wound healing activities localized around tumors.