Abstract B14: Activin A regulates cell interactions in the microenvironment of oral squamous cell carcinomas

Abstract

Abstract Although the molecular mechanisms by which carcinoma-associated fibroblasts (CAFs) influence oral squamous cell carcinomas (OSCC) remain largely unknown, previous studies demonstrated that presence of CAFs in the stroma of OSCCs is an important risk factor of patient's shortened survival. Here we showed that activin A is produced in higher levels by CAFs compared to normal oral fibroblasts, and that activin A released by CAFs significantly increases OSCC cell proliferation and xenograft tumor volume, whereas down-regulation of activin A decreases OSCC proliferation. Furthermore, activin A reduced OSCC cell death even when challenged by staurosporine, and promoted migration, invasion and the expression of epithelial-mesenchymal transition (EMT) markers (decreases E-cadherin and increases vimentin and N-cadherin) of OSCC cells. Immunohistochemical analysis of 115 OSCC samples revealed that increased activin A expression is significantly correlated with presence of regional metastasis (N stage, p=0.034), poorly differentiated tumors (p=0.013) and shown to be predictive of a shortened disease-free survival (HR: 1.74, 95% CI: 1.39-2.97, p=0.016). Importantly, immunohistochemical expression of activin A was significantly associated with presence of occult lymph node metastasis (p=0.006), which has an important impact on clinical management and prognostication of patients with OSCCs. In conclusion, our data demonstrate that activin A is an important molecule for OSCCs, and its pleiotropic effects on proliferation and invasion are important on control of the aggressiveness of OSCCs. Citation Format: Ricardo D. Coletta, Andreia Bufalino, Lays M. Sobral, Priscila C. Rodrigues, Edgard Graner, Luis P. Kowalski, Tuula Salo. Activin A regulates cell interactions in the microenvironment of oral squamous cell carcinomas. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B14. doi:10.1158/1538-7445.CHTME14-B14