Activation ratio of MMP-2 and expression of MT1-MMP are correlated in thymic epithelial tumours.
OBJECTIVE
To study the relationships between the activation of pro-MMP-2 and the mRNA levels of MT1-MMP and TIMP-2 in thymic tissues and thymic epithelial tumours.


METHODS
We examined the mRNA expressions of MMP-2, MT1-MMP and TIMP-2 with real-time reverse transcription-polymerase chain reaction (RT-PCR). The gelatinolytic activity and MMP-2 activation ratio of thymic tissues, thymomas, and thymic carcinomas were determined with gelatin zymography. The cellular localisation of MMP-2 was detected with film in situ gelatin zymography. We then examined the mRNA expression of MMP-2 in the epithelial tumour cells or lymphocytes and stromal cells distant from the tumour (obtained from two invasive thymomas) using laser-capture microdissection (LCM).


RESULTS
The mRNA levels of MMP-2, MT1-MMP and TIMP-2 were significantly increased from thymic tissue, Stage I-II, III-IV thymomas to thymic carcinomas (p<0.005). They were also significantly increased from AB-B1 (lymphocyte rich and mixed types), B2-B3 (cortical and predominantly polygonal cells types) thymomas to thymic carcinomas (p<0.05). The MMP-2 activation ratio also had the same tendency among the above groups (p<0.05) and was directly correlated to MT1-MMP and TIMP-2 mRNA expression (Spearman rank correlation: r = 0.8627, r = 0.8314; p<0.005). Film in situ zymography demonstrated that positive expression is mainly localised in tumour cell nests and adjacent stroma cells. LCM and real-time RT-PCR results confirmed that the expression of MMP-2 was higher in epithelial tumour cells than in lymphocytes and stromal cells.


CONCLUSIONS
MMP-2, MT1-MMP and TIMP-2 mRNA expression levels were correlated with clinical stages and histological subtypes of thymic epithelial tumours. The activation of pro-MMP-2 might be mediated by MT1-MMP and TIMP-2 up-regulation.
Wang
Yan
Y
Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang 110001, China.
Xu
Hong-Tao
HT
Ueda
Yoshimichi
Y
Shimasaki
Miyako
M
Wang
En-Hua
EH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D005260:Female; D006801:Humans; D007834:Lasers; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000096:biosynthesis*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D042282:Microdissection; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013953:Thymus Neoplasms / Q000378:metabolism* / Q000473:pathology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14