Systemic effects of cytokines released by gene-transduced tumor cells: Marked hyperplasia induced in small bowel by γ-interferon transfectants through host lymphocytes

P. L. Lollini, A. D'Errico, C. De Giovanni, L. Landuzzi, F. Frabetti, G. Nicoletti, F. Cavallo, M. Giovarelli, W. F. Grigioni, P. Nanni

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Abstract

Cells transduced with cytokine genes are currently used to enhance the anti-tumor and immunomodulatory effects of these molecules in cancer therapy. The sustained release of cytokine thus obtained can perturb many homeostatic systems of the host. We have previously shown that the murine mammary adenocarcinoma TS/A transfected with the murine γ-interferon (IFN-γ) gene stimulates a strong immune response that impairs tumor growth. Mice bearing tiny tumors have serum IFN-γ levels constantly exceeding 100 IU/ml. Therefore, we asked which systemic effects can be triggered in mice by such transfectants. BALB/c mice bearing tumors produced by clone 16.6000 cells (which release 6,000 IU/ml of IFN-γ in culture) were compared to normal mice and to mice with tumors produced by parent cells transfected with the neomycin resistance gene (NEO cells, no IFN-γ release). Histological studies revealed a marked hyperplasia of small bowel in mice bearing 16.6000 tumors; the villi and crypts of these mice were >1.5 times longer than those of normal mice and of mice bearing NEO tumors. In vivo administration of bromodeoxyuridine evidenced a 2.5-3 times increase in the proliferative score of the intestinal crypts of mice bearing 16.6000 tumors compared to control mice. No intestinal alterations were observed in nude mice bearing 16.6000 tumors. T lymphocytes thus appear to play a causal role in this phenomenon.

Original languageEnglish
Pages (from-to)425-430
Number of pages6
JournalInternational Journal of Cancer
Volume61
Issue number3
Publication statusPublished - 1995

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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