Lymphocyte and monocyte-induced motility of MCF-7 cells by tumor necrosis factor-alpha.
A potentially important tumor-host interaction is increased tumor-cell invasiveness in response to motility factors derived from stromal and lymphoid cells. Conditioned medium of IL-2-stimulated lymphocytes and fractions enriched in either T cells, natural killer (NK) cells, or monocytes induced motility in MCF-7 breast carcinoma cells. ELISA and antibody neutralization studies demonstrated that this effect was due to tumor necrosis factor-alpha (TNF-alpha) secretion by the lymphoid cells or the enriched fractions. Unstimulated leukocytes in direct contact with MCF-7 cells also induced motility that was inhibited by anti-TNF-alpha antiserum. Time-lapse video microscopy of cells exposed to 10 ng/ml TNF-alpha showed that motility was independent of its toxic effects. Immunoperoxidase showed that MCF-7 cells expressed both the 55-kDa and the 75-kDa TNF-alpha receptors (TNFR). Antiserum against the 55-kDa TNFR, like TNF-alpha, induced motility in MCF-7 cells. This was most likely due to cross-linking of the 55-kDa TNFR monomers, since the monomeric F(ab) did not produce this effect. Our results raise the possibility that TNF-alpha-induced motility is one mechanism by which tumor cells overcome the potential anti-tumor immune function of lymphocytes and macrophages in peri-tumoral infiltrates.
Carpenter
P M
PM
Department of Pathology, University of California, Irvine 92868, USA. pmcarpen@uci.edu
Gatanaga
T
T
Nguyen
H P
HP
Hiserodt
J C
JC
D001943:Breast Neoplasms / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects*; D018920:Coculture Techniques; D003432:Cross-Linking Reagents / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D018715:Microscopy, Video; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D003432:Cross-Linking Reagents; D017077:Culture Media, Conditioned; D007376:Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha