Expression of serotonin receptors and role of serotonin in human prostate cancer tissue and cell lines

BACKGROUND: Increase in the number of serotonin (5-HT) releasing neuroendocrine (NE) cells has been shown to be correlated with tumor progression, loss of androgen dependence, and poor prognosis. Serotonin is a well-known mitogen which mediates a wide variety of physiological effects via multiple receptors, of which receptor subtype 1 (5-HTR1) has been identified in prostate cancer (PC) cell lines. Recently, 5-HT has been found to show growth-promoting activity and to be functionally related to oncogenes. MATERIALS AND METHODS: Localization, protein content, and mRNA expression of 5-HTR subtype 1A, 1B, and 1D was studied in prostatic tissue (35 patients), metastases, PC cell lines, a benign prostatic stromal cell line (human prostate cell preparation (hPCP)), and xenografts of PC-3 cells by immunohistochemistry (IHC), Western blotting, and RT-PCR, respectively. The growth-inhibition effect of a 5-HT1A antagonist (NAN-190) on PC cell lines was studied using a bromodeoxyuridine (BrdU) assay. RESULTS: A strong immunoreaction of 5-HTR1A and 1B was demonstrated in high-grade tumor cells (35/35) and a small number of BPH cells, whereas 5-HTR1D was confined to vascular endothelial cells. 5-HTR1A was also demonstrated in PC cells metastasized to lymph node and bone, PC-3, DU145, LNCaP, and in xenografts of PC-3 cells and hPCP. Western blot analysis gave strong bands from PC tissue extracts compared to BPH tissue. Using RT-PCR, 5-HTR1A mRNA was demonstrated in all PC cell lines. An antagonist of 5-HTR1A (NAN-190) inhibited the growth of PC-3, DU145, and LNCaP cells but not of hPCP cells. CONCLUSIONS: This is the first study demonstrating an overexpression of 5-HTR subtypes 1A and 1B in PC cells, especially in high-grade tumors. Moreover, 5-HT stimulates proliferation of PC cells and 5-HTR1A antagonists inhibit proliferation. Thus, we propose that 5-HT has an important role in tumor progression, especially in the androgen-independent state of the disease. The design of specific antagonists for this type of receptor might be useful for the growth control of androgen-independent tumors.     

The effect of serotonin and serotonin antagonists on bladder cancer cell proliferation

OBJECTIVE: To investigate the role of serotonin (5-hydroxytryptamine, 5HT) and its antagonists in the proliferation of high-grade bladder cancer cells (HT1376), as high-grade bladder cancer has a rapid rate of progression, invasion and recurrence, and 5HT antagonists inhibit the growth of the prostate cancer cell line (PC3). MATERIALS AND METHODS: HT1376 (human grade III transitional cell carcinoma) cells were incubated with either 5HT or 5HT antagonists (5HT(1A), 5HT(1B), 5HT(1D), 5HT(2), 5HT(3) and 5HT(4)). After 72 h, cell viability was assessed using the crystal violet assay. The presence of 5HT receptor subtypes on HT1376 cells and sections of human bladder cancer tissue was determined by immunohistochemistry and Western blot analysis. RESULTS: 5HT caused a dose-dependent increase in the proliferation of HT1376 cells. The maximum increase in cell proliferation (12%; 12 samples, P < 0.001) was at 10(-8)m as compared to the control at 72 h. At 10(-4)m, 5HT(1A) antagonist (NAN-190 hydrobromide) and 5HT(1B) antagonist (SB224289 hydrochloride) had a 10% (12 samples, P < 0.001) and 93% (12, P < 0.001) inhibitory effect on HT1376 cell growth, respectively, compared to the control at 72 h. There was immunostaining for 5HT(1A) and 5HT(1B) receptors in HT1376 cells and malignant bladder tissue, confirming the presence of these two receptor subtypes. Western blot analysis showed the presence of 5HT(1A) and 5HT(1B) receptor proteins with bands of 46 kDa and 43 kDa, respectively. CONCLUSION: 5HT(1A) and to a greater extent 5HT(1B) antagonists significantly inhibit bladder cancer cell growth. This effect is probably mediated via the 5HT(1A) and 5HT(1B) receptors. These results highlight the potential use of 5HT(1A) and 5HT(1B) antagonists in the treatment of bladder cancer.     

Expression of cyclin DI in human prostate cancer cell lines

Deregulation of cyclin expression has been found in many tumors. In this report, we studied expression of cyclin DI in three human prostate cancer cell lines: the androgen-dependent LNCaP and the androgen-independent PC3 and DU 145 cell lines. Northern blot analysis showed that DU145 and PC3 cells expressed more abundant cyclin DI than LNCaP cells. Southern blot analysis showed no evident gene amplification or rearrangement of cyclin DI in any of these cell lines. Serum starvation and replenishment were used in the cell culture to study the regulation of expression of cyclin DI. Cyclin DI mRNA expression was detected by Northern blot analysis when LNCaP cells grew in medium with serum but was not detected after serum withdrawal; however, cyclin DI mRNA was induced after serum was added. Cyclin DI mRNA expression by PC3 and DU 145 cells was detected both when they grew in medium with serum and after serum withdrawal, although expression decreased greatly after 24 hours in the PC3 cell line. Immunoprecipitation and immunohistochemical staining also showed that cyclin D I protein was always expressed in PC3 and DU 145 cells under different growth factor environment, whereas it decreased significantly in LNCaP cells deprived of serum and the level resumed again when serum was re-added. This suggests that expression of cyclin DI is regulated by exogenous growth factors in LNCaP cell line and becomes constitutive in PC3 and DU 145 cell lines.     

The potential role of purine-rich element binding protein (PUR) alpha as a novel treatment target for hormone-refractory prostate cancer

BACKGROUND: Hormonal therapy for advanced prostate cancer is typically effective at first, but almost all men suffer refractory disease which often is life threatening. The nuclear matrix comprises not only of the structural elements of the nucleus, but is associated with many components of the molecular machinery. Our aim is to find novel targets for the treatment of hormone-refractory prostate cancer (HRPC) by focusing on the composition of the nuclear matrix proteins (NMPs). METHODS: LN96 cells were established at our Institution after long-term culturing of LNCaP cells under androgen deprived conditions. The composition of NMPs of LNCaP cells and LN96 cells were analyzed by two-dimensional (2D) electrophoresis and spots differentially expressed were investigated by mass spectrometry for identification. Among the spots identified, we analyzed the potential functional role of the identified proteins in prostate cancer cells by establishing stable overexpressed cells. RESULTS: We found that purine-rich element binding protein (PUR)alpha was significantly repressed not only in NMPs but also in total protein and mRNA levels of LN96 cells in comparison to LNCaP cells under the same steroid deprived conditions. Moreover, PURalpha was decreased in its expression both at the protein and mRNA levels in the androgen-independent prostate cancer cell lines, PC3 and DU145 in comparison to LNCaP cells. Stably overexpressing PURalpha in PC3 and DU145 cells negatively regulates cell proliferation, resulting in decreases in PCNA expression. CONCLUSION: Further dissection of the role of PURalpha in cell growth regulation may reveal a novel target for HRPC.     

Expression and immunolocalisation of neutral endopeptidase in prostate cancer

BACKGROUND: Neutral Endopeptidase (NEP) is a cell surface enzyme that cleaves and inactivates neuropeptides. When present on androgen-dependent prostate cancer (PC) cells, NEP inactivates growth stimulatory neuropeptides. After androgen ablation NEP expression decreases and neuropeptides can enhance cell growth, leading to the development of androgen-independent, neuropeptide stimulated PC. Aim of the study was to analyse the expression, localisation and distribution of NEP in benign and malignant prostatic tissues and its relation to the cytoskeleton. METHODS: Immunohistochemistry (IHC) was performed to localise NEP in fixed specimens from normal prostatic tissue, benign prostate hyperplasia (BPH) and PC of Gleason grade 2-5. In situ hybridisation and Western blotting experiments were carried out to confirm NEP gene expression and translation to mature protein in BPH and PC tissue. Confocal laser scanning microscopy was utilised to investigate whether development of high grade prostate tumours was accompanied by changes in intracellular actin/NEP colocalisation patterns. Finally, the proliferative activity in relation to loss of NEP expression was investigated by dual staining of NEP and Ki-67 in prostatic tumours. RESULTS: In situ hybridisation studies revealed preserved expression of NEP mRNA in epithelial cells of PC. NEP was by IHC shown to be located in the apical plasma membrane of normal epithelial cells and BPH tissue. In PC a Gleason grade dependent shift of the NEP distribution pattern towards a heterogeneous, partly cytoplasmic allocation of the protein was found. Compared to BPH tissue, specimens derived from PC showed very low IHC-staining intensity for NEP protein. In high grade PC the typical apical colocalisation of actin and NEP was lost and a strong granular cytoplasmic NEP staining was found. PC areas with a high expression of NEP displayed diminished proliferative activity i.e. low staining intensity for Ki-67. CONCLUSIONS: NEP is differentially expressed in the normal and the pathologically altered prostate with a clear shift from a membrane bound to a cytoplasmic distribution pattern in high-grade tumours and loss of NEP expression in areas of high proliferative activity. The data presented support an active involvement of NEP in the progression of androgen-independent PC. Further studies are needed to unravel the mechanisms underlying the cytoplasmic NEP distribution in PC.     

ErbB-4 may control behavior of prostate cancer cells and serve as a target for molecular therapy

PURPOSE: To assess ErbB-4 expression in advanced human prostate cancer (PC) cell lines, the role of ErbB-4 in motility, migration, and proliferative/tumorigenic potential of PC cells, and efficacy of anti-ErbB-4 monoclonal antibody (Mab) treatment on PC cells in vitro and tumor growth in vivo. MATERIALS AND METHODS: Established advanced human PC cell lines (PC-3, Cl-1, and Du-145) were evaluated for ErbB-4 expression. Several Cl-1 cell line clones expressing various levels of ErbB-4 were isolated, their motility, migration capacity, and in vitro proliferation as well as survival following Mab treatment were evaluated. Tumorigenicity and proliferation capacity of these clones in vivo and efficacy of Mab treatment on tumor growth were estimated by measurements of subcutaneous tumors developed in nude mice. RESULTS: PC cell lines studied express ErbB-4. Both PC-3 and Du-145 cell lines express high ErbB-4 levels; only 50% of Cl-1 cells express ErbB-4 with large heterogeneity. Cl-1 sub-clones highly expressing ErbB-4 showed increased cell motility, migration, and proliferation rate in vitro and enhanced growth in vivo, compared to clones with low ErbB-4 expression. Mab treatment inhibited the growth of cells expressing high but not low ErbB-4 levels in vitro and decreased the growth of subcutaneous tumors in nude mice generated by ErbB-4 highly expressing cells. CONCLUSIONS: High expression of ErbB-4 in prostate cancer Cl-1 cell clones correlated with high proliferative and migration capacity and high tumorigenic potential. The inhibitory effect of Mab on cell proliferation and on subcutaneous tumor growth suggests ErbB-4's potential as a target for molecular anticancer therapy.     

去泛素化酶3在前列腺癌中的表达及其对前列腺癌细胞生物学特性的影响

［摘要］ 目的 探讨去泛素化酶3在人不同前列腺癌细胞株中与前列腺癌组织中的表达,以及去泛素化酶3对前列腺癌细胞增殖、迁移和上皮间质化的影响。方法 采用Western Blot法和实时荧光定量PCR法,分别检测去泛素化酶3在前列腺癌细胞株和正常前列腺上皮细胞株中的蛋白和mRNA水平。以前列腺癌细胞株PC?3为研究对象,通过瞬时转染siRNA抑制去泛素化酶3的表达,然后采用MTS法和Transwell法分别检测PC?3细胞增殖和迁移能力的变化,最后通过Western Blot法明确去泛素化酶3在前列腺癌细胞中对上皮间质化关键因子Snail1的调控作用。结果 Western Blot法和实时荧光定量PCR均显示去泛素化酶3在前列腺癌细胞中的蛋白和mRNA水平高于正常前列腺细胞株（P<0.05）;通过siRNA抑制去泛素化酶3的表达后,PC?3细胞的增殖能力和迁移能力均明显减弱（P<0.05）,而且Snail1的表达也同时下降。结论 去泛素化酶3在前列腺癌中高表达,具有促进前列腺癌细胞增殖和迁移的作用,并且通过对Snail1去泛素化,可能具有增强前列腺癌细胞上皮间质化的能力,有望成为前列腺癌治疗的新靶点。     

Analysis of the inflammatory network in benign prostate hyperplasia and prostate cancer

INTRODUCTION: The complexity of acute and chronic inflammatory processes may either lead to benign prostate hyperplasia (BPH) and/or prostate cancer. Obviously, various tissue cells are activated by chemokines via different chemotaxin receptors which then trigger subsequent processes in angiogenesis, cellular growth, and extravasation as well as neoplasia. METHODS: Using the surgically obtained tissue of patients (n = 36) with BPH or prostate carcinoma (PCA), we studied among others the expression of chemokines (Rantes, IL-8), chemotaxin receptors (CXCR-3 and -4, CCR-3, CCR-5), of matrixmetalloproteinases (MMP-2 and 9), of Toll-like (TL) receptors 1, 2, 3, 4, 5, 7, and 9 and of the inducible cyclooxygenase-2 (cox-2) by RT-PCR. Further support for the different properties of tissue from PCA was obtained using two different PCA cell lines (PC3 = androgen resistant cell) or LNCAP cells (androgen sensitive) with emphasis on IL-8, Il-6, and PGE(2) release. Cell lines were stimulated with either the tumor necrosis factor-alpha (TNF-alpha) and lipopolysacharide (LPS) over time. In addition to cytokine release, the quantification of mRNA by lightcycler for cox-2, IL-6, and IL-8 was performed on these cell lines. RESULTS: Remarkable differences in expression were obtained by RT-PCR when BPH tissue versus PCA was analyzed. Expression of CXCR-1 after incubation with LPS and TNF-alpha showed time-dependent differences for androgen-sensitive LNCAP as compared to androgen-resistant PC-3 cells. TNF-alpha incubation leads to a time-dependent induction of cox-2 expression unlike to activation with LPS. Differences with regard to cox-2, IL-6, and IL-8 expression were seen by quantitative lightcycler analysis. Significant differences were also observed when TL receptors 4, 5, 7, and 9 were analyzed which were significantly expressed in BPH- as compared to PCA-tissue. CONCLUSIONS: Our data clearly demonstrate that various inflammatory and cell biological cascades are involved which either lead to BPH or can be linked to the development of PCA. The exact cell biological mechanisms may provide novel therapeutic options in the treatment of both diseases.     

Inhibitory effects of digitalis on the proliferation of androgen dependent and independent prostate cancer cells

PURPOSE: Digitalis or cardiac glycosides have been noted to induce tumor static or oncolytic effects in various types of cancer. We evaluated the effects and underlying mechanisms of cardiac glycosides, including digoxin, digitoxin and ouabain, on the proliferation of hormone dependent and independent prostate cancer cell lines. MATERIALS AND METHODS: Cell proliferation of the 3 human prostate cancer cell lines LNCaP, DU145 and PC3 was measured by 3-(4,5-dimethylthiazol-2-yle)2,5-diphenyltetralozium bromide (Sigma Chemical Co., St. Louis, Missouri) colorimetric assay. The cytotoxic effects of digitalis on prostate cancer cells were determined by lactate dehydrogenase measurements of the culture medium. Intracellular Ca2+ was measured by a dual wavelength spectrometer system. The percent of apoptotic cells after digitalis treatment was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling and flow cytometry. RESULTS: Digoxin, digitoxin and ouabain significantly inhibited the proliferation of LNCaP, DU145 and PC3 cells at a dose of 1 or 10 microM. after 1 to 4 days of culture. Cytotoxicity of digitalis on the DU145 and LNCaP cells was dose dependent but cytotoxicity was not obvious in PC3. Digitalis (1 microM.) significantly increased intracellular Ca2+ in LNCaP and DU145 after 12 hours of culture but PC3 cells needed a 24-hour treatment to show any effect. In the apoptosis measurement digitalis at a dose of 1 and 10 microM. also significantly increased the percent of apoptotic cells in the LNCaP, DU145 and PC3 cell lines. Normal control human glomerular epithelial cells showed no response to digitalis treatment at all tested doses. CONCLUSIONS: Digitalis may inhibit the proliferation of prostate cancer cell lines, although the 3 cell lines showed varied sensitivity to digitalis. These effects are possibly the result of a mechanism involving sustained elevation of the concentration of intracellular Ca2+ and of apoptosis.     

Aurora B expression directly correlates with prostate cancer malignancy and influence prostate cell proliferation

BACKGROUND: Chromosomal instability is one of the most common features of prostate cancer (PC), especially in advanced stages. Recent studies suggest that defects in mitotic checkpoints play a role in carcinogenesis. Lack of mitotic regulation induces aneuploidy in cancer cells acting thereafter as a driving force for malignant progression. Serine/threonine protein kinases of the Aurora genes family play an important throughout the entire cell cycle. In that Aurora B regulates chromosome segregation by ensuring the orientation of sister chromatids. As a consequence, the overexpression of Aurora B in diploid human cells NHDF induces the appearance of multinucleate cells. METHODS: Archive samples of normal and neoplastic prostate tissue, and prostate derived cell lines were screened for the expression of Aurora B. RESULTS: Immunohistochemical analysis showed increased nuclear expression of Aurora-B in high Gleason grade PCs respect to low and intermediate grade cases and in all cancers in respect to hyperplastic and normal glands. Furthermore, in the high Gleason grade anaplastic cancer tissues Aurora B expression was accompanied by the phosphorylation of the histone H3. In analogy to the in vivo situation, Aurora B was vigorously expressed in the androgen independent PC cell lines PC3 and DU145, while a very modest expression of the kinase was observed in the androgen sensitive LnCap cells and in the EPN cells, a line of epithelial cells derived from normal prostate tissue. In addition, in PC3 cells Aurora B expression is accompanied the by the phosphorylation of the histone H3. The block of Aurora B expression induced by an inhibitor of Aurora kinase activity significantly reduced the growth of prostate carcinoma cells, but not that of non-transformed EPN cells. CONCLUSIONS: Our data are the first demonstration of a role of Aurora B in PC progression. In addition, the observation that Aurora B specific inhibitors interfere with PC cell proliferation but not with that of non-transformed prostate epithelial cells suggest that Aurora B is a potential therapeutic target for PC.     

表皮生长因子对PC-3细胞内皮素-1及其受体mRNA表达的影响

目的:探讨表皮生长因子(EGF)对激素非依赖性前列腺癌(HRPC)PC-3细胞中内皮素1(ET-1)及其受体mRNA表达的影响。方法:EGF作用不同时间(0、8、16、24、32、48h)后,RT-PCR法测定PC-3细胞中ET-1及其受体ETAR mRNA、ETBR mRNA表达;EGF干预24h后,RT-PCR法测定ET-1及其受体ETAR mRNA、ETBR mRNA表达变化。结果:在PC-3细胞中可检测到ET-1及ETAR mRNA表达,但无ETBR mRNA表达;EGF可上调ET-1及ETAR mRNA表达,与对照组比较,差异具有显著性;ET-1及ETAR mRNA表达随EGF干预时间增加而增加,EGF作用不同时间对PC-3细胞ET-1、ETAR mRNA表达的影响不同,差异具有显著性(P<0.05)。结论:EGF可上调PC-3细胞中ET-1及ETAR mRNA表达,为HRPC的治疗提供了分子生物学基础。     

Effect of extracellular ATP on the growth of hormone-refractory prostate cancer in vivo

OBJECTIVE

To investigate whether the antineoplastic action of ATP on hormone‐refractory prostate carcinoma (HRPC) cells in vitro also occurs in vivo, by examining the effect of ATP in vivo on tumours resulting from implanted HRPC cells in mice.

MATERIALS AND METHODS

HRPC tumour cells DU145 and PC‐3 were implanted into male nude athymic mice. The effect of daily intraperitoneal (i.p.) injections of ATP (25 mm ) on the growth of freshly implanted and established HRPC tumours was assessed. Histological examination using light and electron microscopy was used to confirm retention of the original ultrastructure of the implanted tumours.

RESULTS

Daily i.p. injections of ATP significantly reduced the growth of freshly implanted DU145 tumour by 57.8% (P = 0.003), and reduced the rate of growth of established DU145 tumour by 69.0% (P = 0.006). ATP also significantly reduced the growth of freshly implanted PC‐3 tumour by 68.9% (P < 0.001). ATP treatment had no adverse effects on the host mice.

CONCLUSION

Our results show, for the first time, that ATP effectively reduces the growth of advanced HRPC tumours in vivo. This may represent a step in establishing ATP as an effective agent for HRPC treatment.     

GPC5与前列腺癌发生及预后的关系

目的 探讨磷脂酰肌醇蛋白聚糖-5(GPC5)与前列腺癌发生及预后的关系。方法 选取2013年2月至2015年5月在本院治疗的前列腺癌患者104例(病例组),同时选取良性前列腺增生患者89例作为对照组,采用免疫组化染色法检测GPC5蛋白表达,采用荧光定量PCR检测GPC5 mRNA表达。同时选取高侵袭前列腺癌PC3系细胞、低侵袭LNCaP系细胞以及正常前列腺上皮细胞RWPE-1系细胞,采用western blot检测GPC5蛋白表达。结果 观察组GPC5 mRNA相对表达为(0.64±0.15)和GPC5蛋白阳性表达率为34.62%,明显低于对照组(P<0.05);术前PSA≥4 ng/mL、肿瘤分期为T3、Gleason评分≥8分患者GPC5蛋白阳性表达率分别为20.34%、19.44%和21.05%,明显低于术前PSA＜4 ng/mL、肿瘤分期为T2和Gleason评分＜8分患者(P<0.05);GPC5蛋白阳性表达患者中位总生存时间为39.04个月,明显高于GPC5蛋白阴性表达患者(P<0.05);PC3细胞GPC5蛋白表达为(0.083±0.024),明显低于LNcaP和RWPE-1细胞(P<0.05);LNcaP细胞GPC5蛋白表达为(0.301±0.083),明显低于RWPE-1细胞(P<0.05)。结论 前列腺癌组织GPC5 蛋白及mRNA表达下调,与临床病理特征及预后有关,值得进一步研究。     

Expression of gonadotropin-releasing hormone (GnRH) and GnRH receptor mRNA in prostate cancer cells and effect of GnRH on the proliferation of prostate cancer cells

The purpose of this study was to determine the production of gonadotropin-releasing hormone (GnRH), the co-occurrence of GnRH receptors in prostate cancer cells, and the effect of GnRH on prostate cancer cell proliferation. Four human prostate cancer cell lines were studied. LNCaP is an androgen sensitive prostate cancer cell line, DU-145 and PC-3 are androgen resistant, and TSU-Pr1 is uncharacterized. The expression of GnRH and GnRH receptor mRNAs were assessed by in situ hybridization and the effect of exogenous GnRH on proliferation of prostate cancer cells was measured by thymidine incorporation assay. GnRH mRNA expression, determined by in situ hybridization, was found in 83.48% of the LNCaP, 89.7% of the TSU-Pr1, 86.2% of the PC-3 and 95.3% of the DU-145. Signals of GnRH receptor mRNA were detected in more than 95% of the cells of all four cell lines. The proliferation of the prostate cancer cells grown in media supplemented with peptide hormone lacking charcoal-stripped serum was significantly (P < 0.05) suppressed. No significant effect of GnRH on the proliferation of all four prostate cancer cells was observed. In summary, prostate cancer cells produced GnRH and its receptors, and exogenous GnRH treatment did not affect the prostate cancer cell proliferation. The existence of GnRH and GnRH receptor mRNA in the same cell suggests that the role of GnRH produced by prostate cancer cells would be autocrine. Received: 21 August 1997 / Accepted 15 April 1998     

Down-regulation of prostasin serine protease: a potential invasion suppressor in prostate cancer.

BACKGROUND: Prostasin is a serine protease predominantly expressed in normal prostate epithelial cells. The biological function of prostasin has not been determined. METHODS: Western blot and RT-PCR analyses were used to examine the expression of prostasin in prostate cancer cell lines. Immunohistochemistry was used to evaluate prostasin protein expression in human prostate cancer. An in vitro Matrigel invasion assay was used to test the invasiveness of prostate cancer cell lines forced to express recombinant prostasin. RESULTS: Both prostasin protein and mRNA were found to be expressed in normal human prostate epithelial cells and a non-invasive human prostate cancer cell line, the LNCaP, but neither was found in invasive human prostate cancer cell lines DU-145 and PC-3. Prostasin mRNA expression was absent in invasive prostate cancer cell lines of a transgenic mouse model. Immunohistochemistry analysis showed that prostasin protein expression is down-regulated in high-grade prostate cancer. Transfection of DU-145 and PC-3 cells with a full-length human prostasin cDNA restored prostasin expression and reduced the in vitro invasiveness by 68 and 42%, respectively. CONCLUSIONS: Our data indicate that prostasin may be implicated in normal prostate biology and is able to suppress prostate cancer invasion in vitro.