Bone marrow-derived mesenchymal stem cells (BM-MSCs) home to tumour sites and form part of the tumour stroma. While many studies show that that BM-MSCs are supportive of continuing tumour development, contradictory findings have also been published. Therefore, although these cells are a major influence on the behaviour of the tumour, their impact on the tumour is not well defined.
In vitro, BM-MSC migration and invasion was increased in the presence of breast and colon cancer cells and aspartic acid protease cathepsin D is also part of the chemoattractive mechanism. The enzyme and its precursors are produced by the cancer cells and through an enzymatic mechanism, upregulate BM-MSC movement, but not proliferation or adhesion.
In our in vitro system, media conditioned by BM-MSCs reduced migration and invasion of breast cancer cells. Tissue inhibitor of metalloproteinases-1 and -2 (TIMP-1 and TIMP-2) accumulated around 50-fold over the conditioning period and blocking both TIMP-1 and -2 activity increased breast cancer cell movement back to untreated values. This suggests that, over time, BM-MSCs may have an overall anti-metastatic effect.
In conclusion, proteases and their inhibitors influence both the migration of BM-MSCs towards the tumour microenvironment and the overall effects of BM-MSCs on tumour behaviour.