Expression of tumor-associated trypsinogens (TAT-1 and TAT-2) in prostate cancer.
BACKGROUND
Trypsinogens are pancreatic serine proteinases and expressed in several cancers as tumor-associated trypsinogens (TAT). Trypsin mediates activation of pro-uPA and pro-MMPs, thus promoting angiogenesis and tumor invasion. Recently, we described expression of TAT in the human male genital tract and now we studied TAT in relation to PSA in PCa.


METHODS
TAT expression was studied by immunohistochemistry, in situ hybridization, RT-PCR, DNA-sequencing and IFMA. LNCaP cells were used to study secretion of TAT and PSA after androgen stimulation.


RESULTS
Immunoreactive TAT was localized in all prostatic tumors (n = 109), lymph node (n = 16), and bone metastases (n = 17). Immunostaining intensity increased with higher Gleason's grade, whereas PSA immunostaining decreased significantly. PSA and TAT were not identically distributed in benign and malignant cells. Androgen stimulation of LNCaP cells decreased secretion of TAT and increased that of PSA. TAT mRNA was demonstrated in tissue sections and identified as TAT-1 and -2 by RT-PCR and DNA-sequencing.


CONCLUSIONS
Expression of TAT is better preserved than PSA in high-grade PCa. Expression of TAT and PSA is regulated by different mechanisms as demonstrated in tissue sections and in vitro. Locally produced TAT may act in a paracrine mode to promote angiogenesis and tumor invasion in PCa by both activating and degrading of other proteinases. Further studies on the role of TAT in invasive PCa and on the mechanisms involved in the regulation of TAT expression are warranted.
Bjartell
Anders
A
Department of Urology, Malmö University Hospital, Lund University, Malmö, Sweden. anders.bjartell@kir.mas.lu.se
Paju
Annukka
A
Zhang
Wan-Ming
WM
Gadaleanu
Virgil
V
Hansson
Jens
J
Landberg
Göran
G
Stenman
Ulf-Håkan
UH
D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D019899:Paracrine Communication; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D014357:Trypsin / Q000235:genetics* / Q000378:metabolism*; D014362:Trypsinogen / Q000235:genetics* / Q000378:metabolism*
C064831:PRSS2 protein, human; D015741:Metribolone; D014362:Trypsinogen; C489303:PRSS1 protein, human; D014357:Trypsin; D017430:Prostate-Specific Antigen