Abstract: The inventon relates to antibodies that react with a variant epilope in the extracellular region of a variant CD44 polypeptide, wherein the variant epitope has the amino acid sequence:I S S T I S T T P R A P D H T K Q N Q D W T Q W N P S H S N P EV L L Q T T T R M T D V D R N G T T A Y E G N W N P E A H P P LI H H E H H E E E E T P H S T S T I O A T P S S T T E E T A T QK E Q W F G N R W H E G Y R Q T P R E D S H S T T G T A A A S AH T S H P M Q G R T T P S P E D S S W T D F F N P I S H P M G RG H Q A G R R (residues 53-219 of SEQ ID NO:4). Methods of using the antibodies to identify variant epitopes also are provided.

Abstract: A monoclonal antibody (MAb1.1ASML) directed against a surface glycoprotein of the metastasizing rat pancreatic carcinoma cell line BSp73ASML, was used to identify and isolate a complementary DNA (cDNA) clone capable of encoding for a glycoprotein with partial homology to CD44, a presumed adhesion molecule. This clone, which was subsequently designated pMeta-1, contains an additional extracellular domain of 162 amino acids inserted into the CD44 protein between amino acid positions 223 and 247 (by analogy to human and murine CD44). This new variant was expressed only in the metastasizing cell lines of two rat tumors, the pancreatic carcinoma BSp73 and the mammary adenocarcinoma 13762NF; it was not expressed in non-metastasizing tumor cell lines nor in normal rat tissues. Overexpression of pMeta-1 in the nonmetastasizing BSp73AS cell line suffices to establish full metastatic behavior. The variant-specific rat CD44 sequence was used to isolate a cDNA clone encoding for a human homologue as well.

Abstract: The presence of certain extracellular regions ("ECR") from human and rat variants of the CD44 membrane glycoprotein have been found to be associated with metastasis ability in tumor cells. Isolated polynucleotides encoding the ECRs permit expression of the ECR polypeptide, which in turn can be used as an antigen to obtain monoclonal antibodies that recognize the ECR polypeptide. The anti-ECR monoclonal antibodies have the ability to prevent metastasis by tumor cells that would otherwise metastasize and spread.