The role of neural cell adhesion molecule in the tumorigenicity of multiple myeloma in SCID mice.

Abstract

Neural Cell Adhesion Molecule (NCAM) is a glycoprotein involved in cell adhesion. NCAM is present on multiple myeloma (MM) as determined by immunohistochemistry. Molecular characterization of MM associated NCAM determined that MM expresses the 140 kd form of the molecule and the sequence of a 525bp RT-PCR product is identical to lymphoid associated forms of the molecule. The 8226 Dox40 cell line is 50% positive for NCAM. This cell line was sorted and subsequently cloned into an NCAM negative and NCAM positive population. To determine what role NCAM plays in the pathogenesis of MM SCID mice were injected with these populations. Of the mice that received the NCAM negative cells 19/23 (87%) developed tumors while only 2/23 (9%) of the mice that received NCAM positive tumors developed tumors. Increasing the number of tumor cells injected did not change these results. Injection of two other MM lines, ARH-77 (NCAM negative) and Karpas (NCAM positive) yielded the same results. The differences in tumorigenicity are not due to differences in growth kinetics of the two clones, ability to invade using an in vitro invasion assay or differences in genotype when examined karyotypically or genotypically. SCID mouse NK cells and macrophages are not cytotoxic for the human tumor cells and SCID macrophages are equally cytostatic for the human tumor cells. Neither cell line is able to stimulate the release of H₂O₂ or TNF from the macrophages. To determine what role NCAM plays in the differences in tumorigenicity the NCAM negative cells were transfected with NCAM using the LXSN retroviral vector. Injection of SCID mice with the transfected cells did not alter their tumorigenicity in SCID mice. These results suggest the NCAM may be a useful marker to isolate Multiple Myeloma cells but NCAM plays no role in the tumorigenicity of Multiple Myeloma.