Enhancement of metastatic potential by gamma-interferon.
Preincubation of murine colon 26 colon adenocarcinoma cells with gamma-interferon (IFN-gamma), but not alpha-interferon, produced a significant increase in experimental pulmonary metastases in syngeneic BALB/c and T-cell-deficient BALB/c nude mice. The enhancement was seen after as little as 1 h of exposure to 1 unit/ml of IFN-gamma and persisted for at least 72 h following removal of the cytokine. IFN-gamma exerted its effects by increasing the pulmonary retention of cells during the first 6 h following tumor cell injection. During this period all cells visualized in the lung were trapped in pulmonary capillaries. The enhancement was not due to modulations in class I major histocompatibility complex surface antigen expression; nor was it due to alterations in cell size, adhesion to components of the extracellular matrix in vitro, heterotypic or homotypic adhesion, sensitivity to lysis by activated peritoneal macrophages, osmotic fragility, enhancement of surface class II major histocompatibility complex antigen expression, or enhancement of intercellular adhesion molecule-1 (ICAM-1). Colon 26 was completely resistant to natural killer cell-mediated lysis in vitro, and IFN-gamma did not modulate the ability of colon 26 to form conjugates with isolated splenocytes. In vivo elimination of anti-asialo GM1 + cells increased pulmonary metastasis, and in such mice, there was no longer a difference in metastatic potential between control and IFN-gamma-treated cells. We conclude that low doses of IFN-gamma generated at the site of the tumor by host-infiltrating cells or during cytokine therapy could enhance the survival of tumor cells in the circulation and enhance their metastatic potential.
Kelly
S A
SA
Biological Therapy Laboratory, Imperial Cancer Research Fund, London, England.
Gschmeissner
S
S
East
N
N
Balkwill
F R
FR
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005677:G(M1) Ganglioside; D015870:Gene Expression / Q000187:drug effects; D006028:Glycosphingolipids / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D007065:Idoxuridine / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary / Q000648:ultrastructure; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000473:pathology*; D009857:Oncogenes / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000906:Antibodies; D006028:Glycosphingolipids; D015395:Histocompatibility Antigens Class I; D007457:Iodine Radioisotopes; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D007371:Interferon-gamma; D007065:Idoxuridine