Hydroxamate-type matrix metalloproteinase inhibitor batimastat promotes liver metastasis.
Overexpression of matrix metalloproteinases (MMPs) facilitates tumor cell invasion. Synthetic MMP inhibitors such as batimastat have been designed to treat cancer. We report that because of batimastat treatment, human breast carcinoma cells metastasized to the liver in nude mice and that an increase of liver metastases of murine T-cell lymphoma cells was observed in syngeneic mice. Batimastat treatment also caused liver-specific overexpression of MMPs-2, -9, and mRNA up-regulation of angiogenesis factors and caspase-1, even in tumor-free animals. Induction of organ-specific side effects need to be taken into account regarding further development and clinical use of synthetic MMP inhibitors.
Krüger
A
A
Klinische Forschergruppe der Frauenklinik, Institut für Experimentelle Onkologie und Therapieforschung der Technischen Universität München, Munich, Germany. achim.krueger@lrz.tu-muenchen.de
Soeltl
R
R
Sopov
I
I
Kopitz
C
C
Arlt
M
M
Magdolen
V
V
Harbeck
N
N
Gänsbacher
B
B
Schmitt
M
M
D043925:Angiogenesis Inducing Agents / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D020170:Caspase 1 / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology / Q000556:secondary*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000556:secondary; D016399:Lymphoma, T-Cell / Q000201:enzymology / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000633:toxicity*; D011480:Protease Inhibitors / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013876:Thiophenes / Q000633:toxicity*; D015854:Up-Regulation / Q000187:drug effects
D043925:Angiogenesis Inducing Agents; D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D012333:RNA, Messenger; D013876:Thiophenes; D010649:Phenylalanine; C080985:batimastat; D020170:Caspase 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9