Expression of arginase II in prostate cancer

Abstract

Previous reports have shown elevated arginase activity in prostate cancer patients. This study was designed to compare expression levels of arginase II (AII) in various human prostate cancer cell lines and tissues. Expression levels of AII and other enzymes involved in arginine metabolism were examined in androgen-dependent (LNCaP, LAPC-4) and androgen-independent (PC3, DU145, CL-1, CL-2) prostate cancer cell lines by real-time RT-PCR and Western blot analysis. Further expression analysis of AII was accomplished by immunohistochemical staining of a tissue microarray comprised of 246 primary prostatectomy specimens. In addition, polyamine levels were measured within the prostate cancer cell lines by HPLC. Total polyamines were significantly lower in the androgen-dependent cell lines compared to the androgen-independent cell lines. AII expression was found to be most prominent in the androgen-dependent cell lines and least prominent in the androgen-independent cell lines. Additionally, we found expression of ornithine aminotransferase (OAT), an enzyme also responsible for ornithine production, to be inversely correlated with AII expression. The tissue microarray data revealed that the highest AII expression was seen in BPH, followed by PIN and normal samples, with the lowest expression levels observed in prostate cancer tissues. Moreover, we observed an expression gradient across Gleason grades revealing stronger AII expression in low-grade tumors. The polyamine data, combined with the expression analysis studies, support a possible correlation between AII, OAT, and polyamine synthesis. Based on these results, arginase II expression may play a role in prostate cancer progression. More specifically, the elevated AII expression seen in androgen-dependent and in more differentiated prostate cancers suggests that AII could be a potentially useful marker of early stage prostate adenocarcinoma.

Arginase in retinopathy

“…Arginase activity and arginase II expression have been shown to be increased in breast, colon and prostate cancers (Buga et al, 1998; Mumenthaler et al, 2008; Singh et al, 2000). Arginase increases ornithine levels which can enhance cell replication through polyamine synthesis.…”

Reprogramming the tumor microenvironment: tumor-induced immunosuppressive factors paralyze T cells

“…Therefore, elevated levels of arginase and iNOS deplete arginine, an essential nutrient of T cells, from the tumor microenvironment. 9,71 Various types of tumors exhibit elevated arginase and iNOS levels, [72][73][74][75][76] and MDSCs recruited by tumor cells into the tumor microenvironment 78,79 have been shown to produce arginase. 75,79,80 Arginine depletion by increased levels of arginase leads to downregulation of z-chains on T-cell receptors 80,81 and is associated with cell cycle arrest of T cells 72,82 (for review, see ref.…”

Forced LIGHT expression in prostate tumors overcomes Treg mediated immunosuppression and synergizes with a prostate tumor therapeutic vaccine by recruiting effector T lymphocytes

“…IDO has become a gene of interest because expansion of Tregs has previously been shown to be induced in the presence of IDO, leading to immune tolerance against TAA (40). Arg-2 is known to be highly elevated in cancer patients with aggressive tumors (39,41,42); therefore, reduction in both IDO and Arg-2 expression can potentiate a better prognosis. Although we saw a reduction in Arg-2 and IDO in the Ad-LIGHT treated group, we conclude this is an adenovirus-mediated effect because vector controls also displayed a decreased expression of Arg-2 and IDO.…”