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- Title
Tumour-site-dependent expression profile of angiogenic factors in tumour-associated stroma of primary colorectal cancer and metastases.
- Authors
Kahlert, C; Pecqueux, M; Halama, N; Dienemann, H; Muley, T; Pfannschmidt, J; Lasitschka, F; Klupp, F; Schmidt, T; Rahbari, N; Reissfelder, C; Kunz, C; Benner, A; Falk, C; Weitz, J; Koch, M
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Publication
British Journal of Cancer, 2014, Vol 110, Issue 2, p441
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/bjc.2013.745