Collagen I provides a survival advantage to MD-1483 head and neck squamous cell carcinoma cells through phosphoinositol 3-kinase signaling

Background: Head and neck squamous cell carcinoma (HNSCC) has a 50% relapse rate. The tumor microenvironment has been linked to resistance of cancer cells to chemotherapy. We hypothesized that the tumor matrix proteins collagen and fibronectin play protective roles in HNSCC. Materials and Methods: We investigated the effects of collagen I, collagen IV and fibronectin on growth, 2-D and 3-D clonogenic potential, resistance to paclitaxel, apoptosis and activation of phosphoinositol-3 kinase (PI3K) in MD-1483 HNSCC cells. Results: Collagen I, collagen IV and fibronectin specifically increased the efficiency of 2-D colony formation through binding integrins α2β1 and α5β1, respectively, and provided resistance to paclitaxel-induced colony elimination and apoptosis. Collagen I, but not fibronectin, increased the efficiency of 3-D colony formation and induced resistance to paclitaxel. Activation of protein kinase-B by collagen I was necessary for the protective effect. Conclusion: These data support the potential contribution of fibronectin and collagen to chemotherapy resistance in HNSCC, with effects of collagen mediated by PI3K.