Preoperative radiotherapy and extracellular matrix remodeling in rectal mucosa and tumour matrix metalloproteinases and plasminogen components.
BACKGROUND. Preoperative radiotherapy reduces recurrence but increases postoperative morbidity. The aim of this study was to explore the effect of radiotherapy in rectal mucosa and rectal tumour extracellular matrix (ECM) by studying enzymes and growth factors involved in ECM remodeling. MATERIALS AND METHODS. Twenty patients with short-term preoperative radiotherapy and 12 control patients without radiotherapy were studied. Biopsies from rectal mucosa and tumour were collected prior to radiotherapy and at surgery. Tissue MMP-1, -2, -9, TIMP-1, uPA, PAI-1, TGF-beta1 and calprotectin were determined by ELISA. Biopsies from irradiated and non-irradiated peritoneal areas were also analysed. RESULTS. Radiotherapy increased the tissue levels of MMP-2 and PAI-1 in both the rectal mucosa and tumours while calprotectin and uPA showed an increase only in the mucosa after irradiation. The increase of calprotectin was due to an influx of inflammatory cells as revealed by immunohistochemistry. Prior to irradiation, the tumour tissues had increased levels of MMP-1, -2, -9, total TGF-beta1, uPA, PAI-1 and calprotectin compared to mucosa, while TIMP-1 and the active TGF-beta1 fraction showed no statistical difference. CONCLUSIONS. This study indicates a radiation-induced effect on selected ECM remodeling proteases. This reaction may be responsible for early and late morbidity. Interference of this response might reduce these consequences.
Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. eva.angenete@vgregion.se
Eva
E
Angenete
Tom
T
Oresland
Peter
P
Falk
Michael
M
Breimer
Ragnar
R
Hultborn
Marie-Louise
ML
Ivarsson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D005109:Extracellular Matrix / Q000201:enzymology / Q000528:radiation effects*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects* / Q000601:surgery; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism / Q000528:radiation effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism / Q000528:radiation effects; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism / Q000528:radiation effects; D020782:Matrix Metalloproteinases / Q000378:metabolism* / Q000528:radiation effects; D008875:Middle Aged; D010960:Plasminogen Activators / Q000378:metabolism* / Q000528:radiation effects; D011183:Postoperative Complications / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D011300:Preoperative Care; D011446:Prospective Studies; D011878:Radiotherapy / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000528:radiation effects; D016896:Treatment Outcome
D039841:Leukocyte L1 Antigen Complex; D053773:Transforming Growth Factor beta1; D010960:Plasminogen Activators; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1