title: Neutrophils Activate Tumoral CORTACTIN to Enhance Progression of Orohypopharynx Carcinoma.
abstract: 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.
authors: Department of Otorhinolaryngology, University Hospital Essen, University of Duisburg-Essen Essen, Germany.
authors: Claudia A
authors: CA
authors: Dumitru
authors: Agnes
authors: A
authors: Bankfalvi
authors: Xiang
authors: X
authors: Gu
authors: Wilfried E
authors: WE
authors: Eberhardt
authors: Reinhard
authors: R
authors: Zeidler
authors: Stephan
authors: S
authors: Lang
authors: Sven
authors: S
authors: Brandau
keywords: cancer-related inflammation; clinical outcome; head and neck cancer; tumor microenvironment; tumor migration