News and Articles on Health. Medical research topics.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy that may involve the oral cavity, pharynx, larynx, and paranasal sinuses. The mechanisms of tumor progression underlying the clinical behavior of HNSCC remain unclear. CD44 comprises a family of transmembrane receptors that can give rise to multiple CD44 variant isoforms. Hyaluronan (HA), a major extracellular matrix component is the primary ligand for CD44 receptors. HA and CD44 signaling play an important role in HNSCC progression. Several CD44 variant isoforms (including v3-, v6-, and v10-containing isoforms) are associated with advanced disease, possibly through unique growth factor interactions with binding domains in the inserted variant regions of the cytoplasmic domain of CD44. In HNSCC, HA mediates the formation of a complex including CD44 and the epidermal growth factor receptor (EGFR) which is overexpressed in a large proportion of HNSCCs. Downstream effectors under EGFR regulation are activated, promoting promote cell growth and tumor survival. The leukemia-associated Rho-guanine nucleotide exchange factor (LARG) also associates with CD44 and EGFR to promote several Ras and RhoA pathway effectors, leading to cell migration, growth, and tumor survival. The secretion of matrix metalloproteinases, necessary for tumor cell invasion, is also regulated by these HA/CD44-mediated pathways. Finally, EGFR-mediated pathways play major roles in the HA/CD44 promotion of chemoresistance in HNSCC. Understanding HA/CD44-mediated signaling pathways may lead to improved treatment of HNSCC.

Head and neck squamous cell carcinoma (HNSCC) is a malignancy that may involve the oral cavity, pharynx, larynx, and paranasal sinuses. It is the sixth most common cancer worldwide. Advanced HNSCC is an aggressive disease, associated with major morbidity and mortality. The 3-year survival rate for patients with advanced-stage HNSCC treated with standard therapy is only 30%–50%.1 Resistance to standard therapy continues to be a limiting factor in the treatment of HNSCC. Nearly 40% to 60% of HNSCC patients subsequently develop locoregional recurrences or distant metastases.There is a great need to clarify the mechanisms of tumor progression underlying the clinical behavior of HNSCC.

CD44 comprises a family of transmembrane receptors found on many different benign and malignant cells. The human gene (CD44) contains 19 exons. Up to 10 exons (primarily exons 6 through 14) may be alternatively spliced to give rise to multiple variant CD44 isoforms (eg, CD44 v3, CD44 v6, CD44 v10, etc) that, along with standard CD44 (CD44s; ∼85-kDa isoform with no variable exons), make up the CD44 class of receptors. Alternative splicing and post-translational modifications are tightly regulated and permit expression of multiple different CD44 isoforms. The many splicing possibilities of the variable exons of CD44 could in theory give rise to a vast number of CD44 variants, although relatively few have been described to date. Various CD44 variant isoforms are differentially expressed in normal and malignant cells, and confirmation of CD44 isoform expression in HNSCC is well documented, in both tissue specimens and established cell lines.