Problems with RHAMM A New Link between Surface Adhesion and Oncogenesis?

transformation and metastasis formation when overex-pressed in immortalized murine fibroblasts (Hall et al., 1995). Based on the published cDNA sequence, we raised three polyclonal antibodies recognizing different epi-In a quite spectacular report, a novel mechanism of cell topes in human and murine RHAMM proteins, each of transformation was proposed: a matrix receptor linked which only recognizes either an 85 kDa protein in ex-by a GPI anchor to the outer surface of the plasma tracts of human cells (Assmann et al., 1998) or a single membrane, called RHAMM (receptor for hyaluronic acid 95 kDa protein in extracts of immortalized murine cells mediated motility), acted as a dominant oncogene and and primary tissues (Hofmann et al., 1998; Fieber et al., was required for transformation (Hall et al., 1995). This 1998; see Figure 1). We also isolated additional se-finding stimulated subsequent investigations that have quences at the 5Ј end of the murine RHAMM cDNA revealed significant inconsistencies with the original (Hofmann et al., 1998) that share high homology with study and with several other. The aim of this letter is to the 5Ј end of the newly isolated human RHAMM cDNA clarify these discrepancies and to stimulate discussion clones (Wang et al., 1996; Assmann et al., 1998). The on this controversial issue. new 5Ј sequences are encoded by additional exons that RHAMM was originally identified as a 56–58 kDa hyal-are contiguous with " RHAMM " genomic sequences uronate-binding protein present in the supernatant of (Fieber et al., 1998; see Figure 1). Ectopic expression of murine fibroblasts and fibrosarcoma cell lines (Turley our full-length murine cDNA in human fibroblasts leads et al., 1987). A polyclonal antibody raised against this to the expression of the 95 kDa protein only (Hofmann protein stained structures on the cell surface (Turley et et al. A exclusively disappears (unpublished data). Finally, ex-first cDNA sequence for murine RHAMM, which con-tensive RT-PCR analyses of various tissues fail to detect tained an open reading frame encoding a 52 kDa poly-alternatively spliced RNAs or variation in the expression peptide, was isolated using this polyclonal antibody of the v4 exon (exon 8). Taken as a whole, these data (Hardwick et al., 1992; see Figure 1). However, subse-argue against major splicing-based variation in RHAMM quent studies using antibodies based upon this cDNA gene products. Moreover, they suggest that the RHAMM clone sequence information have recognized numerous cDNA clone used in the above transformation experi-apparent RHAMM …