All these assets make miRNA undoubtedly a very elegant and flexible tool. Conflict of Interests The authors state no conflict of interests. Acknowledgments J. R. Viola was supported by a postdoctoral fellowship

from Bayerischen Forschungsstiftung (PDOK-78-11) and thereafter from Frauenbeauftragte at LMU. D. F. Rafael was supported by a doctoral fellowship of the Portuguese Science Foundation, FCT (SFRH/BD/76270/2011).
CD44 (cluster of differentiation 44) is a widely expressed cell surface Inhibitors,research,lifescience,medical hyaluronan receptor which consists in a single chain transmembrane glycoprotein with a size that varies between 80 and 200kDa. It is moreover an acidic molecule with an isoelectric point between 4.2 and 5.8 [1]. CD44 receptor belongs to the family of cell adhesion molecules (CAMs) together with selectins, integrins, and cadherins. The CAMs control cell behavior by mediating contact between cells or between cells and the extracellular matrix and are essential for Inhibitors,research,lifescience,medical INCB024360 cell line maintaining tissue integrity. Because of these important functions, Inhibitors,research,lifescience,medical they are also involved in pathological conditions including tumor progression and metastasis [2]. It is well known that

various tumors, for example, epithelial, ovarian, colon, stomach, and acute leukemia, overexpress CD44 [3]. CD44 comprise a family of glycoproteins encoded by a single gene located on the short arm of chromosome 11 and composed of 20 exons [4]. Extensive alternative splicing generates multiple variant isoforms of CD44 receptor denoted as CD44v. The most abundant standard isoform of human CD44 protein is the smallest isoform that lacks any variant exons, designated CD44s, but some epithelial cells Inhibitors,research,lifescience,medical also express a larger isoform called CD44E [5]. The expression of CD44 isoforms containing combinations of the other variant exons is far more restricted in normal tissues. In particular, CD44s is abundantly expressed by both normal and cancer cells, whereas the variant CD44 isoforms (CD44v), that contain a variable

number of exon insertions (v1–v10) at the proximal Inhibitors,research,lifescience,medical plasma membrane external region, are expressed mostly by cancer cells. CD44 is endogenously expressed at low levels on various cell types of normal second tissues [6, 7] but requires activation before binding to hyaluronan [8–11]. The CD44 structure of normal cells is distinct from that of cancer cells because pathological conditions promote alternate splicing and posttranslational modifications to produce diversified CD44 molecules with increased tumorigenicity [22, 23]. The effect of native hyaluronan as well as of the catabolic enzymes and the degradation products of this macromolecule on tumor progression is complex. Moreover, the amount of intratumoral hyaluronan also varies depending on the cell type and on the degree of tumor cell differentiation.