Hypoxia and the Tumor Secretome

Abstract

Metastasis remains the leading cause of cancer-related deaths. To date, there are no specific treatments targeting disseminated disease. New therapeutic options will become available only if we enhance our understanding of mechanisms underlying metastatic spread. A large body of literature shows that the metastatic potential of tumor cells is strongly influenced by microenvironmental cues such as low oxygen (hypoxia). Clinically, hypoxia is a hallmark of most solid tumors and is associated with increased metastasis and poor survival in a variety of cancer types. Mechanistically, hypoxia influences multiple steps within the metastatic cascade and particularly impacts the interactions between tumor cells and host stroma at both primary and secondary sites. Here we review current evidence for a hypoxia-induced tumor secretome and its impact on metastatic progression. These studies have identified potential biomarkers and therapeutic targets that could be integrated into strategies for preventing and treating metastatic disease.

Keywords: Blood vessel formation; ECM remodeling; Hypoxia; Immune evasion; Metastasis; Motility; Premetastatic niche; Pro-survival; Secretome; Tumor microenvironment; Vascular permeability.