Enhanced tumor growth and metastatic spread of an mh 134 variant lacking a part of the mm antigen: A possible role of antibody-dependent cellular cytotoxicity in control of tumor growth and metastases
✍ Scribed by Hideki Hara; Ichiro Kawase; Kiyoshi Komuta; Tomiya Masuno; Susumu Kishimoto
- Publisher
- John Wiley and Sons
- Year
- 1989
- Tongue
- French
- Weight
- 807 KB
- Volume
- 44
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
The role of antibody-dependent cellular cytotoxicity (ADCC) in host defense against tumor growth and metastasis was investigated with MH 134, an MM antigen-positive murine hepatoma, and MH 13444, a variant with enhanced tumorigenesis and metastasis, in syngeneic C3H/HeN mice. When inoculated subcutaneously into C3HIHeN mice, MH 1344 tu- mors grew more rapidly than did MH I34 tumors and consistently metastasized to the draining lymph nodes, whereas MH134 tumors did not. Also, MH134-M exhibited a significantly greater lung colonization potential than did MH 134, when inoculated intravenously into C3HIHeN mice. In BALB/c nuhu mice, however, solid MH I34 tumors grew and metastasized to the same extent as MH 134-M, indicating that there is no significant intrinsic difference between these two tiimor lines in proliferative or metastatic capacity. Enzymelinked immunosorbent assay (ELISA) and immunoblotting, performed after SDS-PAGE analysis of cellular extracts with a monoclonal antibody (MAb) that recognizes a part of the HM antigen, revealed that the cells of MH 13444 lack at least a part of the MM antigen. Sera of C3HIHeN mice bearing solid MH I34 tumors were found to contain anti-MM-antigen antibodies, when tested by immunoblotting of SDS-PAGEdeveloped materials. Cytotoxicity testing in which thioglycollate-induced peritoneal macrophages were used as effector cells revealed that antibodies present in sera strongly induced ADCC to MH I34 but not to MH 13444. On the other hand, sera of MH 134-M tumor-bearing C3H/HeN mice neither contained anti-MM-antigen antibodies nor induced ADCC to MH I34 or MH 1344 tumor cells. Intravenous injection of carrageenan into C3H/HeN mice bearing solid MH134 tumors significantly enhanced tumor growth, whereas the growth of subcutaneously injected MH 134-M tumors was not influenced by this treatment. These results suggest that the enhanced tumorigenesis and metastasis of the MHI34-M line in C3HI HeN mice are based, at least in part, on significant loss of the MM antigen and the resultant inability to induce ADCCtriggering antibody production during tumor growth.