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[Cancer Research 51, 4020-4027, August 1, 1991]
© 1991 American Association for Cancer Research

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Enhancement of Metastatic Potential by {gamma}-Interferon

Stephen A. Kelly, Stephen Gschmeissner, Nick East and Frances R. Balkwill1

Biological Therapy Laboratory [S. A. K., F. R. B.] and Electron Microscope Department [S. G.], Clare Hall Laboratories [N. E.], Imperial Cancer Research Fund, P. O. Box 123, Lincoln's Inn Fields, London WC2A 3PX, and Blanche Lane, South Mimms, Hertfordshire EN6 3LD, England

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.

1 To whom requests for reprints should be addressed.

Received 1/11/91. Accepted 5/22/91.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1991 by the American Association for Cancer Research.