Die Laserinduzierte Thermotherapie (LITT) experimenteller Lebermetastasen induziert im Vergleich zur chirurgischen Resektion eine erhöhte mRNA Expression von TIMP-1 in residualem unbehandeltem Tumor mit konsekutiv vermindertem Metastasenwachstum
Objective: It is known that laser-induced thermotherapy (LITT) of liver metastases causes local synthesis of the extracellular matrix (ECM) around the thermally damaged tissue. Of importance here is the induction of specific tissue inhibitors (TIMP = tissue inhibitor of metalloproteinases) of matrix-degrading enzymes (matrix-metalloproteinases = MMP), since they play an essential role in micrometastasis. The aim of the study was to compare metastatic growth of untreated residual tumors after LITT and surgical resection as well as to examine differences in the expression of ECM components.
Material and Methods: Two liver tumors per animal were induced in WAG rats. Only one of the two tumors (therapy tumor) was treated either by LITT (n = 25) or left hemihepatectomy (n = 25). The second tumor was left untreated (control tumor). In the control group (n = 25), both tumors remained untreated. After 24, 48, 96 h and 14 d, 5 animals from each group were killed and the control tumors were measured and cryopreserved. In situ hybridisation was used for mRNA detection of collagen 1, TIMP-1 and MMP-1. Collagen I, III, IV and VI expression was immunohistochemically examined. Tumor proliferation was determined by the anti-BrdU test.
Results: In the laser and resection group, the therapy tumor was completely eradicated (negative BrdU incorporation) in all cases. Control tumor volume in the LITT, resection and control groups did not differ before the intervention (p > 0.01). After 14 d, the control tumor volumes in the LITT group (232 ± 40 mm  were about 5 times smaller than in the resection group (1233 ± 118 mm3) and the control group (978 ± 87 mm3) [p < 0.001 each]. Immunohistochemically, collagen I, III, IV and VI molecules were expressed around the control tumors. Already after 96 h, mRNA expression of TIMP-1 was higher in the LITT group with 93.9 ± 4.6 cells/mf than in the resection group with 72.0 ± 5.0 cells/mf (p < 0.01) and remained clearly higher even after 14 d with 112 ± 10.7 vs. 73.7 ± 2.6 cells/mf (p< 0.001).
Conclusions. 1) LITT reduced the growth of untreated residual tumors compared to surgical resection. 2) Reduced tumor growth after LITT is associated with increased mRNA expression of TIMP-1 in the tumor. 3) LITT-induced local synthesis of the ECM seems to have a suppressive effect on the growth of untreated residual tumor tissue via upregulation of TIMP-1.
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