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Human tongue carcinoma growth is inhibited by selective antigelatinolytic peptides
Author(s) -
Heikkilä Pia,
Suojanen Juho,
Pirilä Emma,
Väänänen Anu,
Koivunen Erkki,
Sorsa Timo,
Salo Tuula
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21540
Subject(s) - carcinoma , tongue , cancer research , medicine , biology , pathology
Abstract Matrix metalloproteinases (MMP‐2 and MMP‐9, or gelatinases) are involved in tongue SCC invasion, metastasis and angiogenesis. We have recently shown that a novel and selective hydrophobic cyclic CTTHWGFTLC (CTT1) peptide is inhibitor for MMP‐2 and MMP‐9 (Koivunen et al ., Nat Biotechnol 1999; 17:768–74). In this study, we demonstrate that both the new hydrophilic derivate GRENYHGCTTHWGFTLC (CTT2) peptide and the CTT1 peptide inhibited specifically the human tongue squamous cell carcinoma (HSC‐3) cell‐derived gelatinolytic activity and in vitro invasion and migration of these cells ( p ≤ 0.049). In situ zymography revealed that both peptides also inhibited clearly almost all of the gelatinolytic activity present in the human tongue SCC tissue sections, indicating that MMP‐2 and MMP‐9 are the major gelatinases detected in the tongue carcinomas. However, CTT2 did not inhibit the type I collagen degradation by human collagenases (MMP‐1, MMP‐8 and MMP‐13). Furthermore, CTT2 reduced the blood vessel density ( p ≤ 0.043) and clearly improved the survival of the mice bearing human tongue carcinoma xenografts ( p ≤ 0.012). Overall, we suggest that CTT1 and CTT2 peptides being selective gelatinase inhibitors with significant anti‐tumor properties could be useful to diminish the invasion and angiogenesis of human tongue carcinomas characterized by enhanced gelatinolytic activity in tumors. © 2005 Wiley‐Liss, Inc.