The cancer cell secretome drives cooperative manipulation of the tumour microenvironment to accelerate tumourigenesis

Cellular secretions are a fundamental aspect of cell–cell and cell–matrix interactions in vivo. In malignancy, cancer cells have an aberrant secretome compared to their non-malignant counterparts, termed the “cancer cell secretome”. The cancer cell secretome can influence every stage of the tumourigenic cascade. At the primary site, cancer cells can secrete a multitude of factors that facilitate invasion into surrounding tissue, allowing interaction with the local tumour microenvironment (TME), driving tumour development and progression. In more advanced disease, the cancer cell secretome can be involved in extravasation and metastasis, including metastatic organotropism, pre-metastatic niche (PMN) preparation, and metastatic outgrowth. In this review, we will explore the latest advances in the field of cancer cell secretions, including its dynamic and complex role in activating the TME and potentiating invasion and metastasis, with comments on how these secretions may also promote therapy resistance.