CD44v3+/CD24- cells possess cancer stem cell-like properties in human oral squamous cell carcinoma.
Authors: Todoroki K, Ogasawara S, Akiba J, Nakayama M, Naito Y, Seki N, Kusukawa J, Yano H
Int J Oncol, 2015;48(1):99-109.
Species: Human
Sample Type: Whole Cells
Application: Flow

CD44 is a ubiquitously expressed protein that is the major receptor for hyaluronan and exerts control over cell growth and migration (1‑3). Human CD44 has a 20 amino acid (aa) signal sequence, an extracellular domain (ECD) with a 100 aa hyaluronan-binding disulfide-stabilized link region and a 325‑530 aa stem region, a 21 aa transmembrane domain, and a 72 aa cytoplasmic domain. Within the stem, ten variably spliced exons (v1‑10, exons 6‑15) produce multiple protein isoforms (1‑3). The standard or hematopoietic form, CD44H, does not include the variable segments (1‑3). Cancer aggressiveness and T cell activation have been correlated with expression of specific isoforms (1, 3). With variable N‑ and O-glycosylation and splicing within the stalk, CD44 can range from 80 to 200 kDa (1). Within the N‑terminal invariant portion of the ECD (aa 21‑220), human CD44 shares 76%, 76%, 86%, 83% and 79% aa sequence identity with corresponding mouse, rat, equine, canine and bovine CD44, respectively. The many reported functions of CD44 fall within three categories (1). First, CD44 binds hyaluronan and other ligands within the extracellular matrix and can function as a “platform” for growth factors and metalloproteinases. Second, CD44 can function as a co-receptor that modifies activity of receptors including MET and the ERBB family of tyrosine kinases. Third, the CD44 intracellular domain links the plasma membrane to the actin cytoskeleton via the ERM proteins, ezrin, radixin and moesin. CD44 can be synthesized in a soluble form (4) or may be cleaved at multiple sites by either membrane-type matrix metalloproteinases, or ADAM proteases to produce soluble ectodomains (5, 6). The cellular portion may then undergo gamma secretase-dependent intramembrane cleavage to form an A beta -like transmembrane portion and a cytoplasmic signaling portion that affects gene expression (7, 8). These cleavage events are thought to promote metastasis by enhancing tumor cell motility and growth (1, 5).

1. Ponta, H. et al. (2003) Nat. Rev. Mol. Cell Biol. 4:33.
2. Screaton, G.R. et al. (1992) Proc. Natl. Acad. Sci. USA 89:12160.
3. Lynch, K.W. (2004) Nat. Rev. Immunol. 4:931.
4. Yu, Q. and B.P. Toole (1996) J. Biol. Chem. 271:20603.
5. Nagano, O. and H. Saya (2004) Cancer Sci. 95:930.
6. Nakamura, H. et al. (2004) Cancer Res. 64:876.
7. Murakami, D. et al. (2003) Oncogene 22:1511.
8. Lammich, S. et al. (2002) J. Biol. Chem. 277:44754.
9. Fox, S.B. et al. (1994) Cancer Res.54:4539.