HYALURONATE-INDEPENDENT METASTATIC BEHAVIOR OF CD44 VARIANT-EXPRESSING PANCREATIC-CARCINOMA CELLS

Several studies have demonstrated a correlation between the expression of CD34 variant isoforms and the ability of tumor cells to metastasiz e. The CD44 proteins carry amino acid sequence moths that confer the a bility to bind to the extracellular matrix component hyaluronate (HA). In this study, we investigated whether a CD44 variant previously show n to stimulate metastasis in a rat pancreatic carcinoma model (BSp73AS ) is capable of binding to HA, and whether such binding is critical fo r metastasis. We show that transfection of this CD44 variant into BSp7 3AS cells increases the HA-binding capacity of the cells in a dose-dep endent 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 surf ace-bound hyaluronidase into metastasizing BSp73AS cells bearing varia nt CD44 efficiently ablated the ability of these cells to bind to HA. However, in metastasis assays, these hyaluronidase-transfected cells s howed patterns of metastasis similar to those of the parental cell lin e. We also show that the HA-binding capacity of a variety of tumor cel ls is not correlated dth their metastatic proclivity, and that an anti body 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 formati on, HA binding by tumor cells is not rate limiting for metastasis in t he BSp73AS system and probably also in other metastasizing tumors. Fur thermore, for metastasis by CD34 variant-expressing BSp73AS cells to o ccur, contact of the CD44 variant protein with a ligand other than HA is required.