Collagen Linearization within Tumors

It is now well appreciated that the tumor microenvironment (TME) surrounding primary tumors impacts tumor growth, progression (invasion and migration), and response to therapy. Broadly speaking, the TME is composed of cells (immune cells, activated fibroblasts, adipocytes, endothelial cells), acellular extracellular matrix (ECM), and cytokines or growth factors, some of which are bound or tethered to the ECM proteins. All these compartments undergo significant changes during tumor development and progression. Changes to the ECM, in particular, can dramatically influence cancer biology. This has stimulated the development of therapies that directly reverse or prevent the structural changes in the TME ECM that facilitate cancer progression. But to do so, in a rational manner, we need to understand how structural changes to tumor ECM arise, are remodeled, and function to facilitate tumor cell invasion and migration that give rise to metastatic disease, which is the main cause of cancer-related deaths. In this issue of Cancer Research, Janjanam and colleagues show that the ratio of WISP1/WISP2 in tumors is critical for ECM collagen fiber linearization and important for metastasis. WISP2 binds ECM collagen directly and can inhibit WISP1-mediated collagen linearization. These new results offer a new approach for targeting the altered collagen ECM in tumors by preventing or reversing collagen linearization.