Examples of soluble agents and modulators in HNC include IL-6, IL-8, plated-derived growth factor (PDGF), beta 2 microglobulin (B2M), cellular communication network factor 2 (CCN2), fibroblast growth factor 19 (FGF19), stromal cell growth factor-beta (SCGF), transforming growth factor-beta 1 (TGF-β1), stromal cell-derived factor 1 (SDF-1) and matrix metalloproteinases (MT-MMPs); these have been found to directly regulate the epithelial–mesenchymal plasticity, proliferation, invasion and migration and even drug resistance in HNSCC cells [81]. Here, CXCL12 is linked to head and neck squamous cell carcinoma.