Radiation induced MMP expression from rectal cancer is short lived but contributes to in vitro invasion.
OBJECTIVE
Matrix metalloproteinase (MMP) activity is increased after radiation. The aims of this study were to assess the time course of this increase and its effects on malignant cell invasion.


METHODS
Colorectal cancer (HCT 116, LoVo, C 170 HM 2, CaCO-2), fibroblast (46-BR.IGI, CCD-18 Co) and fibrosarcoma (HT1080) cell lines were irradiated at 4 gray (4 Gy) and matrix metalloproteinase gene and protein expression examined over a 96 h period by real time polymerase chain reaction and gelatin zymography. Invasion was assessed on Matrigel. Human rectal tumour MMP expression was compared before and after long course radiotherapy.


RESULTS
Radiation increased MMP gene expression of tumour cell lines, and resulted in increased MMP protein activity in the HT1080 line. HT1080 and HCT 116 in monoculture and LoVo in co-culture were more invasive after radiation at 48 h in vitro, but long course radiotherapy did not result in a consistent increase in MMP expression from human rectal tumour biopsies.


CONCLUSIONS
Radiation results in increased MMP expression for a limited time period. This results in an early increase in cell line invasion. Further clinical research is required to clarify if MMP inhibition given perioperatively following radiotherapy decreases local recurrence rates.
Speake
W J
WJ
Academic Unit of Cancer Studies, Queen's Medical Centre, University Hospital, D Floor, West Block, Nottingham NG7 2UH, UK.
Dean
R A
RA
Kumar
A
A
Morris
T M
TM
Scholefield
J H
JH
Watson
S A
SA
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy; D001706:Biopsy; D002460:Cell Line; D045744:Cell Line, Tumor; D002588:Cesium Radioisotopes / Q000627:therapeutic use; D018920:Coculture Techniques; D003094:Collagen; D004338:Drug Combinations; D005347:Fibroblasts / Q000201:enzymology* / Q000473:pathology / Q000528:radiation effects; D005354:Fibrosarcoma / Q000201:enzymology* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects; D007797:Laminin; D020778:Matrix Metalloproteinase 2 / Q000528:radiation effects; D020780:Matrix Metalloproteinase 9 / Q000528:radiation effects; D020782:Matrix Metalloproteinases / Q000528:radiation effects*; D009361:Neoplasm Invasiveness; D011509:Proteoglycans; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000532:radiotherapy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D002588:Cesium Radioisotopes; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D019275:Radiopharmaceuticals; C059485:matrigel; D003094:Collagen; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9