Influence of hypoxia on CD44/CD24 adhesion molecules expression in biopsies and cell lines of benign and malignant salivary gland neoplasm

Abstract

The oxygen supply deterioration in solid tumors promotes genetic instability, makes cancer cells more capable to evading apoptosis, induces the extracellular matrix breakdown, and is correlated with tumors aggressively, tumoral progression and metastasis. A subgroup of neoplastic cells with stem cells features strongly expresses CD44, and such cells have angiogenic potential in vivo. CD24 is the P-selectin receptor and its expression was associated with tumoral progression . However, the correlation between CD44 and CD24 expression in solid tumors has been shown divergent results. The hypoxia influence on Salivary Gland Neoplasms and its correlation with CD44 and CD24 expression is not completely elucidated. The objective of this study is correlate the tumoral hypoxia assessed by HIF-1±, CAIX and GLUT1 expression with adhesion molecules CD44 and CD24 expression in Salivary Gland Neoplasms. At the first, the expression of HIF-1± and CAIX and GLUT1 will be correlated with adhesion molecules CD44 and CD24 expression in neoplastic lesions of salivary glands from formalin fixed paraffin embebbed biopsies(80 cases of pleomorphic adenoma, 20 cases of Warthin tumor, 15 cases of adenoid cystic carcinoma and 15 cases of mucoepidermoid carcinoma) and, subsequently, these results will be correlated with prognostic factors and survival rate. Additionally, the hypoxic microenvironment will be reproduced in vitro with three tumor cell lines derived from salivary glands neoplasm and the expression of HIF-1a, CAIX and GLUT1 and its correlation with CD44 and CD24 expression will be addressed (RT-PCR, Quantitative Real Time-PCR e Western Blotting). In these tumoral cell lines, the expression of hypoxia markers and adhesion molecules will be evaluated in function of time of exposure to hypoxic environment. (AU)