Head and neck squamous cell carcinoma (HNSCC) is a major healthcare problem worldwide affecting more than half a million patients each year. Despite considerable advances in the treatment of HNSCC, a high rate of recurrences aggravates the clinical situation and disease outcomes have only modestly improved. Recent insights show that cancer is not only a disease of the transformed epithelium but is also influenced and dependent on its stromal environment. In this review we suggest that resident and bone marrow (BM)-derived mesenchymal stem cells (MSCs) are precursors of the stroma associated with HNSCC and contribute to blood- and lymph angiogenesis, modulate the immune system and produce tumor-associated myofibroblasts. In addition, the impact of radiation therapy on the stromal reaction in HNSCC is discussed. Understanding the mechanisms of how MSCs promote invasive growth and metastasis in HNSCC and respond to cancer management strategies is of profound medical importance and will help us to design improved therapeutic protocols.
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