Association of extracellular matrix microarchitecture and three-dimensional collective invasion of cancer cells.

As much as 90% of cancer associated mortality follows metastasis of a primary tumor. Circulating tumor cells (CTCs) and CTC clusters are important for metastasis. Compared to CTCs, CTC clusters formed by collective invasion exhibit a 23-50 fold increase in metastatic potential, but the factors that influence collective invasion are largely unknown. Using well defined three-dimensional matrices and different extracellular matrix (ECM) concentrations, we found that cancer cells were more prone to collective invasion at low ECM concentration. Moreover, despite variation of biological factors, changes in ECM microarchitecture, especially the pore size of the matrix, was correlated with the probability of collective invasion, which indicates that the physical microarchitecture of ECM plays an important role in collective invasion of cancer cells.