Suppression of LNCaP prostate cancer xenograft tumors by a prostate-specific protein tyrosine phosphatase, prostatic acid phosphatase

SUMMARYSetaria cervi, a bovine filarial parasite contains significant acid phosphatase (AcP) activity in its various life stages. Two forms of AcP were separated from somatic extract of adult female parasite using cation exchange, gel filtration and concavalin affinity chromatography. One form having a molecular mass of 79 kDa was characterized as dual specific protein tyrosine phosphatase (ScDSP) based on substrate specificity and inhibition studies. With various substrates tested, it showed significant activity in the order of phospho-L-tyrosine>pNPP>ADP>phospho-L-serine. Inhibition by orthovanadate, fluoride, molybdate, and zinc ions further confirms protein tyrosine phosphatase nature of the enzyme. Km and Vmax determined with various substrates were found to be 16·66 mM, 25·0 μM/ml/min with pNPP; 20·0 mM, 40·0 μM/ml/min with phospho-L-tyrosine and 27·0 mM, 25·0 μM/ml/min with phospho-L-serine. KIwith pNPP and sodium orthovanadate (IC5033·0 μM) was calculated to be 50·0 mM. Inhibition with pHMB, silver nitrate, DEPC and EDAC suggested the presence of cysteine, histidine and carboxylate residues at its active site. Cross-reactivity withW. bancrofti-infected sera was demonstrated by Western blotting. ScDSP showed elevated levels of IgE in chronic filarial sera using ELISA. Underin vitroconditions, ScDSP resulted in increased effector function of human eosinophils when stimulated by IgG, which showed a further decrease with increasing enzyme concentration. Results presented here suggest thatS. cerviDSP should be further studied to determine its role in pathogenesis and the persistence of filarial parasite.

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The usefullness of low-molecular-weight protein tyrosine phosphatase as a prognostic factor in metastatic hormone-sensitive prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.277 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 277-277

Author(s):

Mari Ohtaka ◽

Takashi Kawahara ◽

Masato Yasui ◽

Kouichi Uemura ◽

Shuko Yoneyama ◽

...

Keyword(s):

Prostate Cancer ◽

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Low Molecular Weight ◽

Protein Tyrosine Phosphorylation ◽

Molecular Weight Protein ◽

Protein Tyrosine ◽

Weight Protein ◽

Hormone Sensitive ◽

Low Molecular Weight Protein

277 Background: Protein tyrosine phosphorylation is an important event that is associated with the processes of cellular metabolism. The control of protein tyrosine phosphorylation is regulated by protein tyrosine kinases and protein tyrosine phosphatases (PTP). Thus, these proteins can control diverse processes like cell proliferation, adhesion, and migration. Recent studies revealed the importance of PTP in the oncogenic process, especially, the significance of low-molecular-weight protein tyrosine phosphatase (LMW-PTP) as a prognostic factor in early prostate cancer. In this study, we evaluated the significance of expression of LMW-PTP in metastatic hormone-sensitive prostate cancer (mHSPC) as a prognostic biomarker. Methods: We identified consecutive 48 men with mHSPC. The prostate cancer tissues obtained by needle biopsies were immunohistochemically stained for LMW-PTP. A pathologist blindly evaluated the expression of LMW-PTP and intensity of staining was classified into two groups, high (diffusely strongly positive) and low (at least focally weak-negative). The correlations between clinicopathological characteristics including age, initial PSA levels, Gleason scores, T stage, N stage, extend of disease on bone scan (EOD), and expression of LMW-PTP and overall survival (OS) were analyzed by multivariate analysis using cox proportional hazards regression model. Results: Median age was 70.0 years and median initial PSA level was 85.4 ng/mL. Gleason scores were 6-7 in 16 patients (33.4%) and 8-10 in 32 patients (66.6%). Clinical T stages were T2-3 disease in 34 patients (70.8%) and T4 in 14 patients (29.2%). Clinical N stages were N0 disease in 21 patients (43.7%) and N1 in 27 patients (56.3%). EOD grades were 0 in 13 patients (27.0%), 1 in 12 patients (25.0%), 2 in 14 patients (29.2%), 3 in 8 patients (16.7%), and 4 in 1 patient (2.1%). Multivariate analysis revealed that Gleason score (≥ 8 vs ≤ 7; HR: 5.795, 95%CI: 1.266-26.520, p = 0.024) and LMW-PTP expression (high vs low; HR: 2.736, 95%CI: 1.035-7.232, p = 0.042) were independent prognostic factors for OS. Conclusions: LMW-PTP might be a potential biomarker to predict overall survival for men with mHSPC.

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