Brittany G. Sullivan, MD
Resident
University of California - Irvine General Surgery
Long Beach, California, United States
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Advancing the treatment of peritoneal carcinomatosis (PC) requires effective and reproducible pre-clinical platforms to test novel drug combinations. The VMT is an in vitro, 3-D platform that emulates a human tumor microenvironment (TME) by creating a microphysiological system that employs human stromal cells, tumor cells and a vascularized environment. We sought to create a colorectal PC VMT model that allows for drug testing studies to be done in an efficient and cost-effective manner.
Methods:
PC xenografts were created by intraperitoneal injection of human peritoneal metastatic colon cancer cells (COLO205) into Balb/c nude mice. Mouse PC tumors were digested into a single cell suspension and transduced with green fluorescent protein. Human endothelial cells and fibroblasts were mixed with the GFP tumor cells in suspension with fibrinogen and thrombin and loaded into the microfluidic device to create the VMT. Tumor growth was monitored with fluorescent intensity measurements using Image J software. VMTs were treated with 0.5µM (n=8), 1µM (n=8), and 4µM (n=8) Mitomycin C (MMC) on day 5 for 48 hours and were compared to untreated (n=8) VMT devices.
Results:
Effective establishment of a 3-D TME was seen after loading of endothelial cells, PC tumor cells and fibroblasts (Figure A). A robust vascular network was established after day 3, establishing a gravity induced “blood flow” to the tumor cells (Figure B,E). Successful tumor progression was confirmed by increase in fluorescent intensity measurement from the PC cells from day 3 to day 11 (0.0018 to 0.012, Figure B-D). PC VMTs treated with 4µM MMC showed the largest decrease in fluorescent intensity measurement on day 11 compared to untreated PC VMTs (0.008 vs. 0.011, Figure E-G).
Conclusions:
We have successfully developed a novel PC VMT model that recapitulates TME and will be used to test novel drug regimens to treat PC. Work is ongoing to compare the ability of this in vitro model to predict treatment responses with that of an animal PC model.