TY  - JOUR
AU  - Kahlert, C.
AU  - Pecqueux, M.
AU  - Halama, Niels
AU  - Dienemann, H.
AU  - Muley, T.
AU  - Pfannschmidt, J.
AU  - Lasitschka, F.
AU  - Klupp, F.
AU  - Schmidt, T.
AU  - Rahbari, N.
AU  - Reissfelder, C.
AU  - Kunz, Christina
AU  - Benner, Axel
AU  - Falk, C.
AU  - Weitz, J.
AU  - Koch, M.
TI  - Tumour-site-dependent expression profile of angiogenic factors in tumour-associated stroma of primary colorectal cancer and metastases.
JO  - British journal of cancer
VL  - 110
IS  - 2
SN  - 1532-1827
CY  - Edinburgh
PB  - Nature Publ. Group
M1  - DKFZ-2017-02743
SP  - 441 - 449
PY  - 2014
AB  - Tumour-associated stroma has a critical role in tumour proliferation. Our aim was to determine a specific protein expression profile of stromal angiogenic cytokines and matrix metalloproteinases (MMPs) to identify potential biomarkers or new therapy targets.Frozen tissue of primary colorectal cancer (n=25), liver (n=25) and lung metastases (n=23) was laser-microdissected to obtain tumour epithelial cells and adjacent tumour-associated stroma. Protein expression of nine angiogenic cytokines and eight MMPs was analysed using a multiplex-based protein assay.We found a differential expression of several MMPs and angiogenic cytokines in tumour cells compared with adjacent tumour stroma. Cluster analysis displayed a tumour-site-dependent stromal expression of MMPs and angiogenic cytokines. Univariate analysis identified stromal MMP-2 and MMP-3 in primary colorectal cancer, stromal MMP-1, -2, -3 and Angiopoietin-2 in lung metastases and stromal MMP-12 and VEGF in liver metastases as prognostic markers (P>0.05, respectively). Furthermore, stroma-derived Angiopoietin-2 proved to be an independent prognostic marker in colorectal lung metastases.Expression of MMPs and angiogenic cytokines in tumour cells and adjacent tumour stroma is dependent on the tumour site. Stroma-derived MMPs and angiogenic cytokines may be useful prognostic biomarkers. These data can be helpful to identify new agents for a targeted therapy in patients with colorectal cancer.
KW  - Angiogenesis Inducing Agents (NLM Chemicals)
KW  - Angiopoietin-2 (NLM Chemicals)
KW  - Biomarkers, Tumor (NLM Chemicals)
KW  - Cytokines (NLM Chemicals)
KW  - VEGFA protein, human (NLM Chemicals)
KW  - Vascular Endothelial Growth Factor A (NLM Chemicals)
KW  - Matrix Metalloproteinases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:24292449
C2  - pmc:PMC3899771
DO  - DOI:10.1038/bjc.2013.745
UR  - https://inrepo02.dkfz.de/record/126715
ER  -