Hyaluronate-independent metastatic behavior of CD44 variant-expressing pancreatic carcinoma cells

Jonathan P. Sleeman, Sigrid Arming, Jürgen F. Moll, Armin Hekele, Wolfgang Rudy, Larry S. Sherman, Günther Kreil, Helmut Ponta, Peter Herrlich

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    73 Scopus citations

    Abstract

    Several studies have demonstrated a correlation between the expression of CD44 variant isoforms and the ability of tumor cells to metastasize. The CD44 proteins carry amino acid sequence motifs that confer the ability to hind to the extracellular matrix component hyaluronate (HA). In this study, we investigated whether a CD44 variant previously shown to stimulate metastasis in a rat pancreatic carcinoma model (BSp73AS) is capable of binding to HA, and whether such binding is critical for metastasis. We show that transfection of this CD44 variant into BSp73AS cells increases the HA- binding capacity of the cells in a dose-dependent manner. Transfection of the same CD44 variant isoform into BDX2 cells also conferred strong HA-binding properties on these cells, but was insufficient to cause them to metastasize. Transfection of a surface-hound hyaluronidase into metastasizing BSp73AS cells bearing variant CD44 efficiently ablated the ability of these cells to bind to HA. However, in metastasis assays, these hyaluronidase-transfected cells showed patterns of metastasis similar to those of the parental cell line. We also show that the HA-binding capacity of a variety of tumor cells is not correlated with their metastatic proclivity, and that an antibody previously shown to block metastasis of the pancreatic carcinoma cells does not interfere with their ability to bind to HA. We conclude that although CD44 variant expression does promote metastasis formation, HA binding by tumor cells is not rate limiting for metastasis in the BSp73AS system and probably also in other metastasizing tumors. Furthermore, for metastasis by CD44 variant-expressing BSp73AS cells to occur, contact of the CD44 variant protein with a ligand other than HA is required.

    Original languageEnglish (US)
    Pages (from-to)3134-3141
    Number of pages8
    JournalCancer Research
    Volume56
    Issue number13
    StatePublished - Jul 1 1996

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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  • Cite this

    Sleeman, J. P., Arming, S., Moll, J. F., Hekele, A., Rudy, W., Sherman, L. S., Kreil, G., Ponta, H., & Herrlich, P. (1996). Hyaluronate-independent metastatic behavior of CD44 variant-expressing pancreatic carcinoma cells. Cancer Research, 56(13), 3134-3141.