CORTACTIN is an
actin-binding protein critically involved in cellular migration and invasion. Here, we investigated the role of
CORTACTIN in the pathophysiology of orohypopharynx
carcinoma - one of the major subtypes of
head and neck cancer. To this end, we analyzed
CORTACTIN expression in
tumor tissues from 89 orohypopharynx
carcinoma patients in relation to clinical parameters. We found that high tumoral
CORTACTIN expression associated with poor survival, higher T-stage, and higher
lymph node metastasis (N-stage) in these patients. Next, we combined the prognostic values of tumoral and stromal cell
biological parameters in our patient cohort. We determined the potential interaction of tumoral
CORTACTIN with
tumor-infiltrating neutrophils, which have been previously linked to poor clinical outcome in orohypopharynx
carcinoma patients with advanced disease. Interestingly, we found that patients with both high tumoral
CORTACTIN expression and high neutrophilic infiltration had significantly worse clinical outcome than all other patients in our cohort. These findings suggest that tumoral
CORTACTIN and
tumor-infiltrating neutrophils might be functionally linked during progression of orohypopharynx
carcinoma. In vitro, we showed that neutrophils released soluble factors which phosphorylated
CORTACTIN in the
tumor cells and promoted their migration. Furthermore, we demonstrated that strong
CORTACTIN phosphorylation significantly correlated with strong neutrophilic infiltration in
tumor tissues from orohypopharynx
carcinoma patients. Taken together, our findings unravel a novel mechanism of
tumor-stroma interaction, which might be relevant for a more accurate prognosis and improved therapeutic strategies in this
tumor entity.