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. 2000 Nov 22;83(11):1538–1543. doi: 10.1054/bjoc.2000.1487

Exploiting changes in the tumour microenvironment with sequential cytokine and matrix metalloprotease inhibitor treatment in a murine breast cancer model

K A Scott 1, H Holdsworth 1, F R Balkwill 1, S Dias 1
PMCID: PMC2363423  PMID: 11076665

Abstract

The study of treatment-induced changes in the tumour microenvironment might lead to effective combinations of biological therapy. IL-12 induced tumour regression and cure of an experimental murine breast cancer, HTH-K, but only after long-term treatment that was associated with chronic toxicity. During IL-12 therapy, tumour levels of the matrix metalloprotease MMP-9 declined and its inhibitor TIMP-1 was strongly induced. We therefore administered alternate cycles of IL-12 and the MMP inhibitor Batimastat (BB94) to mice. Therapeutic efficacy was increased compared with short-term IL-12 therapy but without the chronic toxicity associated with long-term IL-12 treatment. Image analysis of treated tumours revealed that BB94 prevented regeneration of tumour and stromal compartments that normally occurred after short-term IL-12 therapy. © 2000 Cancer Research Campaign http://www.bjcancer.com

Keywords: IL-12, MMP-9, TIMP-1, BB94, MMPI, mammary carcinoma

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Selected References

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