We present a three-dimensional model based on acellular scaffolds to recreate bladder
carcinoma in vitro that closely describes the in vivo behavior of
carcinoma cells. The integrity of the basement membrane and
protein composition of the bladder scaffolds were examined by
Laminin immunostaining and LC-MS/MS. Human primary bladder
carcinoma cells were then grown on standard monolayer cultures and also seeded on the bladder scaffolds. Apparently,
carcinoma cells adhered to the scaffold basement membrane and created a contiguous one-layer epithelium (engineered micro-
carcinomas (EMCs)). Surprisingly, the gene expression pattern displayed by EMCs was similar to the profile expressed by the
carcinoma cells cultured on
plastic. However, the pattern of secreted
growth factors was significantly different, as
VEGF, FGF, and PIGF were secreted at higher levels by EMCs. We found that only the combination of factors secreted by EMCs, but not the
carcinoma cells grown on
plastic dishes, was able to induce either the pro-inflammatory phenotype or the myofibroblast phenotype depending on the concentration of the secreted factors. We found that the pro-inflammatory phenotype could be reversed. We propose a unique platform that allows one to decipher the paracrine signaling of bladder
carcinoma and how this molecular signaling can switch the phenotypes of fibroblasts.