Transforming growth factor β as regulator of cancer stemness and metastasis

Abstract

Key elements of cancer progression towards metastasis are the biological actions of cancer stem cells and stromal cells in the tumour microenvironment. Cross-communication between tumour and stromal cells is mediated by secreted cytokines, one of which, the transforming growth factor β (TGFβ), regulates essentially every cell within the malignant tissue. In this article, we focus on the actions of TGFβ on cancer stem cells, cancer-associated fibroblasts and immune cells that assist the overall process of metastatic dissemination. We aim at illustrating intricate connections made by various cells in the tumour tissue and which depend on the action of TGFβ.

Figure 1

Pleiotropic effects of TGFβ in the tumour microenvironment. Representation of a primary tumour with cancer stem cells (CSCs) or metastasis-initiating cells (light green) and the bulk of the tumour cells (orange). Different cell types surrounding the tumour mass can positively contribute to tumour progression, invasiveness and metastatic dissemination, acting on the tumour cells but also receiving input from the tumour cells (bi-directional arrows). Cells that can inhibit tumour progression are linked to the tumour mass with a negative arrow. The contributions of TGFβ and additional cytokines and chemokines are highlighted next to each arrow. As graphic simplification, haematogenous or lymphatic metastatic dissemination shows solely CSCs co-migrating with stromal cells and platelets. At the secondary site, metastatic colonisation and growth is shown; whether stromal cells dissociate from the metastasising clonal population or whether they are replaced by new local stromal cells is currently unknown (?).