Type IV collagenase (matrix metalloproteinase-2 and -9) in prostate cancer.
BACKGROUND
The type IV collagenases/gelatinases matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) play an important role in cancer invasion and metastasis. In the present study, we measured the expression of mRNAs and enzymatic activities of MMP-9 and -2 in prostate tissues and serum samples from men with or without prostate cancer.


METHODS
A total of 44 tissue samples (three from healthy volunteers, 21 from patients with benign prostate hyperplasia, 10 from patients with localized prostate cancer and 10 from patients with metastatic disease) and 71 serum samples were collected (20 from healthy volunteers, 26 from patients with benign prostatic hyperplasia, 10 from patients with localized cancer, 15 from patients with metastatic cancer). The level of mRNA for MMP-2 and -9 was determined by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The enzymatic activity of MMPs was determined by zymography.


RESULTS
Expression of MMP-9 mRNA was significantly higher in malignant than in nonmalignant prostate tissues (P < 0.001), while no significant difference of MMP-2 expression was detected in different prostate tissues. Results of zymography showed that there was significant difference in the enzymatic activity of MMP-9, but not MMP-2, among normal prostate, BPH, localized and metastatic prostate cancer tissues, serum samples (P < 0.05). The active form of MMP-2, with a molecular mass of 62 kDa, was detected in normal prostate, BPH and prostate cancer tissues, but not in the serum samples. Moreover, there was a significant difference in the ratio of the active form (62 kDa) and proform (72 kDa) of MMP-2 among normal, BPH and prostate cancer tissues. This ratio was further increased in metastatic prostate cancer tissues.


CONCLUSIONS
The activity of MMP-9 and the ratio of active form/proform of MMP-2 are associated with the progression and metastasis of prostate cancer.
Zhang
L
L
The Key Laboratory of Bioactive Materials, Ministry of Education, Institute for Molecular Biology, Nankai University, Tianjin 300071, P.R. China. zhangju@nankai.edu.cn
Shi
J
J
Feng
J
J
Klocker
H
H
Lee
C
C
Zhang
J
J
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000201:enzymology / Q000235:genetics; D009367:Neoplasm Staging; D011467:Prostate / Q000201:enzymology; D011470:Prostatic Hyperplasia / Q000097:blood / Q000201:enzymology / Q000235:genetics; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000556:secondary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9