Louis, MO). as I and I/II. The typical Compact disc44s and a distinctive v6-formulated with CD44 types (Compact disc44v6-10) were discovered in all tissues examples by RT-PCR evaluation. Immunohistochemically, using an antibody that cross-reacted with all Compact disc44 species, Compact disc44 was localized towards the cell surface area, lacuna wall structure and intracellular area from the chondrocytes in the centre and deep area of regular cartilage, aswell much like cells through the entire neoplastic masses. Having an antibody particular for v6-formulated with CD44 types, the variant types was discovered throughout cells of the middle and deep zone of normal cartilage, and localized selectively to intracellular positions. In neoplastic masses, v6-containing CD44 species were found associated only with cells in the hyaline-like cartilage, but not in the fibrocartilaginous regions. Thus a differential expression of the v6-containing CD44 species in the neoplastic masses containing both hyaline-like cartilage and fibrocartilaginous regions was observed when compared to its homogenous expression in normal hyaline cartilage. An involvement between the lack of the variant CD44 (v6-containing) and altered tissue phenotype (e.g., fibrocartilaginous) is ID 8 suggested. INTRODUCTION CD44, a transmembrane glycoprotein on hyaline cartilage chondrocytes, reported to be a cell surface receptor for hyaluronan.23 Evidence has identified an association of neoplasms with expression of the alternative RNA-spliced variant, v6-containing CD44 species.10,13,18 Neoplasms of cartilage are a heterogeneous mix of cartilage tumors that exhibit a wide range of clinical and biological features. Although the extracellular matrix produced by cartilage neoplasms is similar to that produced by normal chondrocytes,4,28,29,38 the over-synthesis of the extracellular matrix in the tumors represents an interesting derangement of normal matrix homeostasis.27 With cartilage consisting of a hyaluronan-rich extracellular matrix and with CD44 having the ability to interact with hyaluronan,23 the potential exists for altered expression of CD44 isoforms to play a role in extracellular matrix integrity in neoplasms. The human CD44 gene has been characterized as 20 exons spanning 50 kilobases of DNA.2 This gene produces a family of receptors of different sizes through alternative RNA splicing. The most common isoform of CD44, identified initially in lymphocytes, is encoded from exons 1 through ID 8 5, VGR1 15 through 17, and 19 ID 8 and is designated as CD44s (standard). CD44s has been shown to have a myriad of functions, including lymphocyte homing and activation, cell adhesion and migration, inhibition ID 8 of cell proliferation, and growth factor regulated cellular proliferation activation.13,16,17,18,26,44 Data also support a role in extracellular matrix maintenance, as CD44s has been shown to mediate hyaluronan uptake in alveolar macrophages,6 type A synoviocytes,1 and chondrocytes.15 In contrast to CD44s, the function(s) of alternatively RNA spliced, variant (v) CD44 species remains largely speculative. These variant CD44 species are generated by insertion of different combinations of 10 exons, 5a (v1) through 14 (v10) into the encoded extracellular domain of the molecule.20,43 Much of the interest in these alternatively RNA-spliced variants centers on a suspected role in tumor progression. In a rat model, monoclonal antibodies against variant sequences (homologous to human exon 10, v6) reacted to metastasizing cell lines but not to their non-migratory counterparts.12 Furthermore, the same researchers reported that transfection of constructs containing the v6 sequence into a non-metastasizing cell line conferred v6 CD44 expression and full malignant behavior to the tumor. Since that discovery, a similar correlation in human tumors has been sought. Increased v6-containing CD44 expression does appear to correlate with tumor growth and more aggressive behavior in some types of cancer, including lymphoma,40 and melanoma,14,30, and colon,7,49 breast,22 and gastric31 cancer. However, the relationship between variant expression and tumor behavior has proven to be more complex than first anticipated.18 The v6-containing CD44 species have been identified in many normal tissues, especially those of epithelial origin.8,14,26 In endometrial and epithelial squamous tumors, a down regulation of v6-containing CD44 expression appears to be associated with malignant transformation.9,41,47 Although expression and function of different species of CD44 have been investigated in a number of cells and tissues, research efforts in cartilage neoplasms have not been reported and the possibility of an association of expression of v6-containing CD44 and loss.