Tenascin-C and fibronectin expression divide early stage tongue cancer into low- and high-risk groups

Whether patients with early-stage oral cancers should be treated with elective neck dissection at the time of the primary surgery or with therapeutic neck dissection after nodal relapse has been a matter of debate.

The extracellular matrix provides a framework for cell adhesion, supports cell movement, and serves to compartmentalize tissues into functional units. Fibronectin is a core component of many extracellular matrices where it regulates a variety of cell activities through direct interactions with cell surface integrin receptors. Fibronectin is synthesized by many adherent cells which then assemble it into a fibrillar network. The assembly process is integrin-dependent and fibronectin-integrin interactions initiate a step-wise process involving conformational activation of fibronectin outside and organization of the actin cytoskeleton inside. During assembly, fibronectin undergoes conformational changes that expose fibronectin-binding sites and promote intermolecular interactions needed for fibril formation. In this review, the main steps of fibronectin assembly are described and recent studies on fibronectin conformational changes are discussed.

The extracellular matrix molecule tenascin-C is highly expressed during embryonic development, tissue repair and in pathological situations such as chronic inflammation and cancer. Tenascin-C interacts with several other extracellular matrix molecules and cell-surface receptors, thus affecting tissue architecture, tissue resilience and cell responses. Tenascin-C modulates cell migration, proliferation and cellular signaling through induction of pro-inflammatory cytokines and oncogenic signaling molecules amongst other mechanisms. Given the causal role of inflammation in cancer progression, common mechanisms might be controlled by tenascin-C during both events. Drugs targeting the expression or function of tenascin-C or the tenascin-C protein itself are currently being developed and some drugs have already reached advanced clinical trials. This generates hope that increased knowledge about tenascin-C will further improve management of diseases with high tenascin-C expression such as chronic inflammation, heart failure, artheriosclerosis and cancer.