Jp. Sleeman et al., HYALURONATE-INDEPENDENT METASTATIC BEHAVIOR OF CD44 VARIANT-EXPRESSING PANCREATIC-CARCINOMA CELLS, Cancer research, 56(13), 1996, pp. 3134-3141
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.