Whole body hyperthermiaによる間質コラゲナーゼ活性の変化と間質リモデリング仮説

Matrix metalloproteinase-1 (MMP-1) has received a considerable attention as one of factors, enhancing tumor infiltration and metastasis. We determined serum levels of MMP-1 and TIMP-2, a tissue inhibitor of metalloproteinase-2 (a protein that suppresses all MMPs activity). Furthermore, we monitored changes in serum levels of MMP-1 and TIMP-2 after Whole Body Hyperthermia (WBH). Samples were collected from 46 patients with advanced cancers and 20 healthy volunteers were also examined for MMP-1 and TIMP-2. Furthermore, they were monitored for 36 patients undergoing one cycle of WBH, three weeks after completion of WBH. Mean serum level of MMP-1 in patients was increased to a significant extent whereas mean serum level of TIMP-2 was markedly lowered, compared to healthy individuals. MMP-1 activity was assessed by MMP-1/TIMP-2 ratio, and the ratio was 0.43 for cancer patients and 0.15 for healthy individuals, thus showing that cancer patients exhibited an apparently higher MMP-1/TIMP-2 ratio than healthy individuals. MMP-1 activity was nearly normalized in 9 responders after WBH, i .e ., from 0.37 (before) to 0.21 (after), whereas MMP-1 activity was increased from 0.43 (before) to 0.51 (after) in 27 non-responders. MMP-1 activity was increased approximately by 3-fold in patients, compared to healthy individuals. MMP-1 activity was normalized in WBH-responders.