Mesenchymal stromal/stem cells in tumour initiation, progression and therapy

The expanding study of mesenchymal stromal/stem cells (MSC) in cancer has amounted to a growing understanding of their underlying biology in malignant and non-malignant settings. In addition to supporting homeostasis in nearly all normal tissues, MSCs also serve as stromal support for a diverse set of malignancies, the most studied being ovarian, breast, brain, blood and colorectal cancers. Their ability to localize to and shape the stromal microenvironment of solid tumours or haematologic malignancies results in increased tumour cell growth, metastasis and survival and promotes the enrichment of the cancer stem cell population, all of which contribute to poor patient outcomes. Here we summarize the known roles MSCs have in promoting or inhibiting carcinogenesis. We highlight emerging concepts including epigenetic reprogramming of MSCs to switch from a tumour-suppressive to tumour-supportive phenotype, their role in cancer initiation, and novel mechanisms of immune modulation. We also cover advances in the development of MSC-targeted treatment modalities for cancer therapy. In addition, given their inherent adaptability, we discuss how MSCs are being co-opted as tools for drug delivery and discuss ongoing challenges in MSC-based therapies.