Differential expressions of CD44 variants in tumors affecting the central nervous system

Background: The polymorphic cell adhesion molecule CD44 exists as a family of proteins generated by extensive alternative splicing of the CD44 pre-messenger RNA and marked posttranslational modification. The differential expression of CD44 isoforms in a variety of human cancers has been proposed to influence tumorigenesis and metastasis. In this study, CD44 gene expression was analyzed in primary and metastatic tumors and in cell lines derived from tumors that affect the central nervous system (CNS), including tumors metastatic to the spine. Materials and Methods: Fifty-four samples were subjected to semiquantitative reverse-transcriptase polymerase chain reaction with CD44-specific primers and hybridized individually with probes specific for the CD44 variant (CD44v) exons v3 to v10. Results: Compared with CD44v-positive breast cancer cell lines and CD44v-negative normal brain tissue, CD44v expression was weak in primary brain tumors and cell lines derived from normal brain and tumor tissue. However, high levels of isoforms encoding multiple-variant exons were shown in all metastatic brain tumors. In contrast, tumors metastatic to the spine were virtually negative for CD44v expression. Several rare CD44 isoforms composed of single-variant exons v3, v4, v6, or v9 were identified in primary brain tumors and may reflect their invasive potential or culturability in vitro. Conclusion: These data suggest differential expression of CD44v may substantially influence the end-organ site of metastasis for tumor cells destined for the CNS.