Changes of proteases and proteinase inhibitors in androgen-dependent advanced prostate cancer patients with alpha2-macroglobulin deficiency.

BACKGROUND

It is thought that the quantitative imbalance between proteases and their inhibitors is a causative factor in invasion and metastasis of cancer cells. We previously reported on a number of androgen-dependent advanced prostate cancer (PCa) patients in which serum alpha2-macroglobulin (alpha2M) levels were markedly decreased to < 20 mg/dL (defined as alpha2M deficiency). Anti-androgen therapy is at first generally very effective for androgen-dependent advanced PCa, yielding survival benefits for most patients. In the present study, we evaluated serum levels of PSA, matrix metalloproteinases-2 (MMP-2), alpha2M, and alpha2-plasmin inhibitor (alpha2PI) in advanced PCa patients with or without alpha2M deficiency in order to determine the clinical significance of these proteases and proteinase inhibitors for PCa progression.

METHODS

In this study, 33 PCa patients were diagnosed at the Kitasato University Hospital and compared with 10 healthy controls. PSA and MMP-2 levels were determined by enzyme immunoassay. Measurement of alpha2M was performed by laser-nephelometry, alpha2PI levels were determined by turbidimetric immunoassay.

RESULTS

Serum levels of PSA and MMP-2 in PCa patients with alpha2M deficiency were significantly higher than in patients not alpha2M-deficient. In contrast, serum levels of alpha2M and alpha2PI in these patients were significantly lower than in those not alpha2M-deficient. PSA and alpha2M levels showed an inverse relationship in androgen-dependent advanced PCa with alpha2M deficiency.

CONCLUSIONS

Our findings indicate that the serum levels of these proteases and proteinase inhibitors, which are involved in the invasion and metastasis of PCa, may be indicators of PCa disease progression in addition to PSA levels.