Using a monoclonal antibody (MAb1.1ASML) raised against a surface glycoprotein of the metastasizing rat pancreatic carcinoma cell line BSp73ASML, cDNA clones have been isolated that encode glycoproteins with partial homology to CD44, a presumed adhesion molecule. In one of the clones, pMeta-1, the epitope marks an additional extracellular domain of 162 amino acids inserted into the rat CD44 protein between amino acid positions 223 and 247 (by analogy to human and murine CD44). The new variants are expressed only in the metastasizing cell lines of two rat tumors, the pancreatic carcinoma BSp73 and the mammary adenocarcinoma 13762NF; they are not expressed in the non-metastasizing tumor cell lines nor in most normal rat tissues. Overexpression of pMeta-1 in the nonmetastasizing BSp73AS cells suffices to establish full metastatic behavior.

To characterize cell surface molecules involved in control of growth of malignant lymphocytes, monoclonal antibodies were raised against the human B lymphoblast cell line SKW6.4. One monoclonal antibody, anti-APO-1, reacted with a 52-kilodalton antigen (APO-1) on a set of activated human lymphocytes, on malignant human lymphocyte lines, and on some patient-derived leukemic cells. Nanogram quantities of anti-APO-l completely blocked proliferation of cells bearing APO- polyacrylamide gel electrophoresis (SDS-PAGE) as a main band of 52 kD (Fig. 1). Apart from actin (43 kD), which was nonspecifically precipitated with IgG3, anti-APO-1 specifically immunoprecipitated a minor band of 25 kD. This 25-kD protein might either represent a degradation product or be noncovalently associated with the 52-kD protein.There are two major modes of death in nucleated eukaryotic cells. Necrosis as a result, for example, of complement attack is characterized by swelling of the cells and rupture of the plasma membrane caused by an increase in permeability. Cells that undergo apoptosis, however, show a different biochemical and morphological pattern (2). This pattern corresponds to the one induced by anti-APO-1: condensation of the cytoplasm, membrane blebbing (Fig. 2a) (1988). 18. DNA fragments without GREs were inserted into the Xba I site (see Fig. 2) of -33 GRE6, displacing the GRE cassette to -262, -366, and -1069 bp from the start of transcription. Weak receptor-mediated activation was detected when GREs were situated at -262, but no effect was observed from the more distal sites.

A variant of the glycoprotein CD44 (CD44v) that shares sequences with variants causally involved in metastasis formation is transiently expressed on B and T lymphocytes and macrophages after antigenic stimulation and in the postnatal period. Antibodies to the variant hinder in vivo activation of both B and T cells. The observation that a protein domain that is expressed on CD44 and required for the lymphatic spread of tumor cells can catalyze an essential step in the process of lymphocyte activation supports the idea that metastasizing tumor cells mimic lymphocyte behavior.