Paracrine Signaling from a Three-Dimensional Model of Bladder Carcinoma and from Normal Bladder Switch the Phenotype of Stromal Fibroblasts

Abstract

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.

The role of cancer-associated fibroblasts in bladder cancer progression

“…Shi et al presented a 3D microfluidic co-culture device to reconstruct an in vivo -like TME for the investigation of CAFs and BCa cells interactions [ 7 ]. Camargo et al [ 76 ] developed a 3D model based on acellular scaffolds to recreate BCa in vitro that closely describes the in vivo behavior of tumour cells. This 3D BCa model may provide a novel platform for elucidating the paracrine signaling of BCa and how this molecular signaling can alter the phenotypes of fibroblasts.…”