Molecular forms of prostate-specific antigen and the human kallikrein gene family: A new era

McCormack, Robert; Wang, T.J.; Rittenhouse, Harry G.; Wolfert, Robert L.; Finlay, Jessica; Lilja, Hans; Okoloff, Roger L.; Öesterling, Joseph E.

doi:10.1016/s0090-4295(99)80076-4

Cited by 285 publications

(143 citation statements)

References 92 publications

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“…Pro-PSA is the latent form of the PSA enzyme and has to be activated extracellularly by the action of specific proteases, most probably kallikrein-2, -4 or -5 [8][9][10] The serum PSA test measures total PSA, which consists of all immunodetectable PSA, comprised mostly of free uncomplexed PSA and PSA bound to the protein inhibitor a1-antichymotrypsin (ACT). 11 It also detects pro-PSA, internally cleaved PSA, but not PSA bound to a 2 -macroglobulin. Different molecular forms of PSA may have different functions.…”

Section: Introductionmentioning

confidence: 99%

PSA affects prostate cancer cell invasion in vitro and induces an osteoblastic phenotype in bone in vivo

Cumming

Hopmans

Vukmirović-Popović

et al. 2011

Prostate Cancer Prostatic Dis

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BACKGROUND:Patients with advanced prostate cancer frequently have a poor prognosis as a result of metastasis and present with high serum PSA levels. There is evidence suggesting that the serine protease activity of PSA could be involved in the invasion and metastasis of prostate cancer. In this study, we determined the effects of PSA and its precursor, pro-PSA, on invasion and the type of bone metastasis. METHODS:We stably transfected prostate adenocarcinoma cells, human DU-145 and rat MatLyLu, with either the fulllength prepro-PSA sequence or pre-PSA DNA, to generate subclones of cells that secrete pro-PSA or free PSA, respectively. Secretion of PSA was measured by western blot analysis and enzyme-linked immunosorbent assay (ELISA). The invasive and migratory properties of the cells were determined using a basement membrane extract and were compared with corresponding empty vector control cells. Twelve days after injection of PSA-secreting MatLyLu cells into the femora of nude mice, bone tumor burden and histomorphometry were determined using a stereological technique. RESULTS:The transfected cells secreted 0.15-2.23 ng PSA/10 6 cells/day. Pro-PSA-secreting subclones increased invasion and migration by 24-263%. Conversely, the PSA-secreting subclones significantly reduced both invasion and migration by 59-70%. The divergent effects on invasion and migration observed in pro-PSA-and PSA-secreting subclones indicate that different forms of PSA may have different functions. Intrafemoral injections with PSA-secreting MatLyLu cells resulted in an increase in osteoblastic parameters when compared with non-PSA-secreting subclones as measured by bone histomorphometry. Concomitantly, a decrease in osteoclasts and eroded surface was observed.CONCLUSIONS: Our in vitro data suggest that PSA, dependent on the predominant form secreted, may decrease or increase invasive properties of prostate cancer cells. The in vivo results indicate that PSA in the bone microenvironment may contribute to the osteoblastic phenotype of bone metastasis frequently observed in prostate cancer.

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Section: Introductionmentioning

confidence: 99%

PSA affects prostate cancer cell invasion in vitro and induces an osteoblastic phenotype in bone in vivo

Cumming

Hopmans

Vukmirović-Popović

et al. 2011

Prostate Cancer Prostatic Dis

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show abstract

“…Prostate Specific Antigen (PSA), a 33 kDa serine protease which has already been established as a valuable marker for screening, diagnosis and management of prostate cancer [2,3] has been suggested to have a number of potential roles in breast cancer. PSA, found in a very low but detectable levels in the circulation of women, is likely to be originated from breast tissue [4].…”

Section: Introductionmentioning

confidence: 99%

Serum total PSA and free PSA in breast tumors

et al. 2011

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“…This gene family has contributed two excellent biomarkers (PSA and hK2) that are currently used for diagnosis and monitoring of prostate cancer (1)(2)(3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Immunofluorometric assay of human kallikrein 6 (zyme/protease M/neurosin) and preliminary clinical applications

Diamandis¹,

Yousef²,

Soosaipillai³

et al. 2000

Clinical Biochemistry

117

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Molecular forms of prostate-specific antigen and the human kallikrein gene family: A new era

Cited by 285 publications

References 92 publications

PSA affects prostate cancer cell invasion in vitro and induces an osteoblastic phenotype in bone in vivo

PSA affects prostate cancer cell invasion in vitro and induces an osteoblastic phenotype in bone in vivo

Serum total PSA and free PSA in breast tumors

Immunofluorometric assay of human kallikrein 6 (zyme/protease M/neurosin) and preliminary clinical applications

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