Journal
HISTOCHEMISTRY AND CELL BIOLOGY
Volume 133, Issue 2, Pages 201-211Publisher
SPRINGER
DOI: 10.1007/s00418-009-0661-6
Keywords
Cancer microenvironment; BMP-4; IGF-2; Epithelial-mesenchymal interaction; Cancer-associated fibroblasts
Categories
Funding
- Ministry of Education, Youth and Sport of the Czech Republic [MSM0021620806, NPVII 2B06106, AV0Z50520514]
- Grant Agency of the Czech Republic [304/08/P175]
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Epithelial-mesenchymal interaction between stromal fibroblasts and cancer cells influences the functional properties of tumor epithelium, including the tumor progression and spread. We compared fibroblasts prepared from stroma of squamous cell carcinoma and normal dermal fibroblasts concerning their biological activity toward normal keratinocytes assessed by immunocytochemistry and profiling of gene activation for growth factors/cytokines by microarray chip technology. IGF-2 and BMP-4 were determined as candidate factors responsible for tumor-associated fibroblast activity that influences normal epithelia. This effect was confirmed by addition of recombinant IGF-2 and BMP4, respectively, to the culture medium. This hypothesis was also verified by inhibition experiments where blocking antibodies were employed in the medium conditioned by cancer-associated fibroblast. Presence of these growth factors was also detected in tumor samples.
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