Tumour-stroma interaction: cancer-associated fibroblasts as novel targets in anti-cancer therapy?
Stroma cells, together with extracellular matrix components, provide the microenvironment that is pivotal for cancer cell growth, invasion and metastatic progression. Characteristic stroma alterations accompany or even precede the malignant conversion of epithelial cells. Crucial in this process are fibroblasts, also termed myofibroblasts or cancer-associated fibroblasts (CAFs) that are located in the vicinity of the neoplastic epithelial cells. They are able to modify the phenotype of the epithelial cells by direct cell-to-cell contacts, through soluble factors or by modification of extracellular matrix components. Seminal functional studies in various cancer types, including breast, colon, prostate and lung cancer, have confirmed the concept that fibroblasts can determine the fate of the epithelial cell, since they are able to promote malignant conversion as well as to revert tumour cells to a normal phenotype. This review focuses on characteristic changes of fibroblasts in cancer and provides the experimental background elucidating functional properties of CAFs in the carcinogenic process. A possible implication in lung carcinogenesis is emphasised. Finally, a laser-capture- and microarray-based approach is presented, which comprehensively characterises carcinoma-associated fibroblasts in their in vivo environment for the identification of potential targets for anti-cancer therapy.
Micke
Patrick
P
Ludwig Institute for Cancer Research, Uppsala, Sweden. patrick.micke@licr.uu.se
Ostman
Arne
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D032342:Muscle Cells / Q000187:drug effects / Q000473:pathology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000970:Antineoplastic Agents; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta