Journal
EXPERT OPINION ON THERAPEUTIC TARGETS
Volume 9, Issue 6, Pages 1217-1233Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/14728222.9.6.1217
Keywords
cancer-associated fibroblast (CAF); hepatocyte growth factor (HGF); laser microdissection; microarray; myofibroblast; platelet-derived growth factor (PDGF); stroma; targeted therapy; transforming growth factor (TGF beta 1)
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Stroma cells contribute to the microenvironment that is essential for cancer growth, invasion and metastatic progression. Fibroblasts, often termed myofibroblasts or cancer-associated fibroblasts (CAFs), represent the most abundant cell type in the tumour stroma. The demonstrated tumour-promoting capacities of CAFs has increased the interest to exploit them as drug targets for anticancer therapy. Although single factors, such as platelet-derived growth factor, transforming growth factor-beta 1, hepatocyte growth factor and matrix metalloproteinases have been identified as mediators in the fibroblast tumour interaction, the morphological and functional differences of CAFs compared with their normal counterparts are only incompletely understood. Recently, novel global methods for gene expression profiling were applied to comprehensively characterise CAFs from breast, pancreas, colon and basal cell cancer in their in situ environment. The analysis of different CAF preparations revealed regulated genes that were previously not described in the tumour-stroma context. Additionally, besides a few striking overlaps, the comparison of the gene lists indicates a high level of heterogeneity in the expression pattern of CAFs from different tumour types. Together, these studies emphasise the importance of cross-talk between stromal and malignant cells of the tumour. It is likely that the continued characterisation of this interaction, and the molecular identification of key mediators, will provide insights into tumour biology and suggest novel therapeutic options.
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