Carcinoma-associated fibroblasts promoted tumor spheroid invasion on a microfluidic 3D co-culture device

Abstract

Carcinoma-associated fibroblasts (CAFs) are a key determinant in malignant progression of cancer and represent an important target for cancer therapies. In this work, we present a microfluidic-based 3D co-culture device to reconstruct an in vitro tumor microenvironment and firstly investigate the effect of CAFs on cancer cell invasion in 3D matrix. This device is composed of six co-culture units, which enable parallel co-culture assays to be run in the presence of 3D extracellular matrix. Salivary gland adenoid cystic carcinoma (ACC) cells and CAFs embedded in matrix were co-cultured without direct contact on the device. Communication between ACC cells and CAFs could be established via medium diffused in matrix. It was observed that CAFs promoted ACC cell invasion in 3D matrix in a spheroid fashion, indicating that CAFs play a critical role in cancer invasion. We further demonstrated the effect of MMP inhibitor as an agent against CAF-promoted cancer invasion. This co-culture device reproducibly reflected the in vivo growth and invasion pattern of ACC and recreated the stroma-regulated ACC invasion. Thus, it provides a suitable platform for elucidating the mechanism of CAF-regulated cancer invasion and discovering anti-invasion drugs in a well defined 3D environment.

A microfluidic-based device for study of transendothelial invasion of tumor aggregates in realtime

“…Microfabricated devices have been developed to facilitate both applied and basic research concerning the biology of cells and tissues. [25][26][27][28][29] The successful reconstitution of organ-level lung tissue on a microfluidic chip indicates that biomimic microsystems could potentially serve as replacements for animal testing. 28 Reconstruction of a blood vessel model has received particular attention in microfluidic technology as variable-sized channels are easily created to mimic vessel cavities.…”

Microgels on-demand

“…For example, an array of microgels with different shapes might be formed to evaluate the relationship between the geometry of the environment and cell fate and behaviour 16,52 , or an array of microgels featuring different composites might be used to evaluate multi-scaffold chemistries for tissue-engineering applications 53,54 . Further, given the many uses 2-5 of hydrogels for applications outside of tissue engineering, we propose that microgels on-demand may represent a powerful new tool for chemistry, biology, physics, and beyond.…”

Assembly of hydrogel units for 3D microenvironment in a poly(dimethylsiloxane) channel

“…Furthermore, an artificial 3D environment can be used to improve the physiological relevance of cell or tissue and to reduce the gap between the in vitro system and the in vivo state, which emphasizes the importance of 3D environment [2,3]. These features overcome the limitations of conventional in vitro cell culture system and facilitate lots of applications such as in vitro biological study [4][5][6], drug development [7][8][9] and cancer research [10][11][12].…”