High interstitial fluid pressure promotes tumor progression through inducing lymphatic metastasis-related protein expressions in oral squamous cell carcinoma

The present study was carried out to analyze the interstitial fluid pressure (IFP) values in patients with oral squamous cell carcinoma and identify the relationship between the IFP and tumor prognosis. We investigated tumor lymphatic metastasis-related protein (VEGFC, VEGFD and VEGFR3) expressions change on SCC-4 and SCC-9 cells subjected to increased extracellular pressure in vitro and analyzed the relationship between these proteins and IFP, and prognosis of patients with oral squamous cell carcinoma. The results showed that the elevated extracellular pressure significantly resulted in a dramatic increase of VEGFC, VEGFD and VEGFR3 protein expressions in OSCC. More important, the activation of VEGFC, VEGFD and VEGFR3 proteins through IFP elevation contributed to poor prognosis for patients with OSCC. These results suggest an important potential clinical application of measuring IFP, which can be used as a generic marker of prognosis evaluation and response to therapy. Furthermore, VEGFC, VEGFD and VEGFR3 may be useful targets in developing novel and specific therapeutic tool for OSCC patients with high IFP.