Matrix composition modulates vasculature formation and intravasation in tumor chip

Have you ever encountered the question: what extracellular matrix (ECM) should I use? Specifically, the choice of matrix is very important to mimic the tumor-stromal cells interaction during cancer intravasation. This paper by Agrawal et al. from the Moeendarbary lab at University College London uses a tumor on a chip to study the effect of different ECM compositions on vasculature formation and cancer cell intravasation.

The authors first studied the effect of different matrices on size and coverage area of the vessels. After adding tumor spheroids, the distance between the vessels and the spheroids increased significantly when they were culture in fibrin compared to other matrices, meaning that adding Matrigel and collagen enhanced the contact between the vessels and the tumor. The presence of tumor decreased the average vessel diameter. Vessel coverage area was larger, with and without tumor, in the presence of all the matrices. Interestingly, cancer cell intravasation occurred only where all the matrix components were present.

The authors used a 3-lane side-by-side chip, added the spheroids (made using human colorectal adenocarcinoma HT29 and human lung cancer cell line A549, and U-bottom plates), matrix (fibrin, fibrin:collagen type I, fibrin:Matrigel, fibrin:collagen type I:Matrigel), endothelial cells (HUVECs) and fibroblasts (normal human lung fibroblasts).
Fabrication method: laser cutting and 3D printing the mold, soft lithography with PDMS
Sterilization method: PDMS device autoclaved, then bonded to glass with plasma, then at 80˚C to restore hydrophobicity
Cell incorporation: Cells and matrix injected via the inlet hole into the central channel
Perfusion/refreshing method: Medium exchange every 24 hours
On-chip read-outs: Immunostaining, vessel perfusion with 70 kDa fluorescent dextran (injection into one side channel only), Fluorescent microscopy

Improvement points
– Use of PDMS
– Manual refreshing of medium
– Manual image analysis

Strong points:
+ Different matrix composition
+ Different cancer types
+ real-time imaging

Conclusion and outlook
A beautiful work emphasizing the importance of choosing the right matrix as the tumor microenvironment in a tumor on a chip. This technology enables researchers to study the effect of tumor microenvironment on cancer metastasis more mechanistically.

Do you have questions about the system in this paper or similar technologies? Or do you want to start with organ on a chip. Feel free to contact us!

Link to paper: https://doi.org/10.1016/j.ooc.2022.100024