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PMID: 24839936 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Differences between CAFs and their paired NCF from adjacent colonic mucosa reveal functional heterogeneity of CAFs, providing prognostic information.

Molecular oncology ·Vol. 8 ·No. 7 ·2014-10-00 ·Pages 1290-305

Berdiel-Acer M, Sanz-Pamplona R, Calon A, Cuadras D, Berenguer A, Sanjuan X, Paules MJ, Salazar R, Moreno V, Batlle E, Villanueva A, Molleví DG

Abstract

Little is known about the difference in gene expression between carcinoma-associated fibroblasts (CAFs) and paired normal colonic fibroblasts (NCFs) in colorectal cancer. Paired CAFs and NCFs were isolated from eight primary human colorectal carcinoma specimens. In culture conditions, soluble factors secreted by CAFs in the conditioned media increased clonogenicity and migration of epithelial cancer cells lines to a greater extent than did NCF. In vivo, CAFs were more competent as tumour growth enhancers than paired NCFs when co-inoculated with colorectal cell lines. Gene expression analysis of microarrays of CAF and paired NCF populations enabled us to identify 108 deregulated genes (38 upregulated and 70 downregulated genes). Most of those genes are fibroblast-specific. This has been validated in silico in dataset GSE39396 and by qPCR in selected genes. GSEA analysis revealed a differential transcriptomic profile of CAFs, mainly involving the Wnt signallingsignalling pathway, focal adhesion and cell cycle. Both deregulated genes and biological processes involved depicted a considerable degree of overlap with deregulated genes reported in breast, lung, oesophagus and prostate CAFs. These observations suggest that similar transcriptomic programs may be active in the transition from normal fibroblast in adjacent tissues to CAFs, independently of their anatomic demarcation. Additionally NCF already depicted an activated pattern associated with inflammation. The deregulated genes signature score seemed to correlate with CAF tumour promoter abilities in vitro, suggesting a high degree of heterogeneity between CAFs, and it has also prognostic value in two independent datasets. Further characterization of the roles these biomarkers play in cancer will reveal how CAFs provide cancer cells with a suitable microenvironment and may help in the development of new therapeutic targets for cancer treatment.

Keywords
Biomarker Carcinoma-associated fibroblasts Colorectal Microenvironment Stroma
MeSH Terms
Animals Cells, Cultured Colon/metabolism,pathology Colorectal Neoplasms/diagnosis,genetics,pathology Fibroblasts/metabolism,pathology Gene Expression Regulation, Neoplastic Humans Mice, Nude Prognosis
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Berdiel-Acer Mireia
Translational Research Laboratory, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, 08908 Catalonia, Spain.
Sanz-Pamplona Rebeca
Biomarkers and Susceptibility Unit, Cancer Prevention and Monitoring Programme, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
Calon Alexandre
Oncology Programme, Institute for Research in Biomedicine IRB, Barcelona, Catalonia, Spain.
Cuadras Daniel
Biomarkers and Susceptibility Unit, Cancer Prevention and Monitoring Programme, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
Berenguer Antoni
Biomarkers and Susceptibility Unit, Cancer Prevention and Monitoring Programme, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
Sanjuan Xavier
Pathology Department, Hospital Universitari de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
Paules Maria José
Pathology Department, Hospital Universitari de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
Salazar Ramon
Medical Oncology Department, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
Moreno Victor
Biomarkers and Susceptibility Unit, Cancer Prevention and Monitoring Programme, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
Batlle Eduard
Oncology Programme, Institute for Research in Biomedicine IRB, Barcelona, Catalonia, Spain.
Villanueva Alberto
Translational Research Laboratory, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, 08908 Catalonia, Spain.
Molleví David G
Translational Research Laboratory, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, 08908 Catalonia, Spain. Electronic address: [email protected].
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Article Info
Journal
Molecular oncology
Abbr.
Mol Oncol
ISSN
1878-0261
DOI
10.1016/j.molonc.2014.04.006
Email
[email protected]
Published
2014-10-00
Epub
2014-00-06
Pages
1290-305
Language
English
Region
United States
NLM ID
101308230
PMCID
PMC5528579
Subset
IM
External Links
PubMed source DOI: 10.1016/j.molonc.2014.04.006 PMC Full Text View journal details
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