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The HDL receptor SR-BI is associated with human prostate cancer progression and plays a possible role in establishing androgen independence.

Schörghofer D, Kinslechner K, Preitschopf A, Schütz B, Röhrl C, Hengstschläger M, Stangl H, Mikula M - Reprod. Biol. Endocrinol. (2015)

Bottom Line: Recent data indicate that elevated cholesterol levels in the plasma are a prerequisite for the progression of prostate cancer.The disease-free survival time was reduced (P = 0.02) in patients expressing high intra-tumor levels of SR-BI.SR-BI mRNA correlated with HSD17B1 and HSD3B1 and SR-BI protein staining showed correlation with active ribosomal protein S6 (RS = 0.828, P < 0.00001).

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria. david.schoerghofer@meduniwien.ac.at.

ABSTRACT

Background: Human prostate cancer represents one of the most frequently diagnosed cancers in men worldwide. Currently, diagnostic methods are insufficient to identify patients at risk for aggressive prostate cancer, which is essential for early treatment. Recent data indicate that elevated cholesterol levels in the plasma are a prerequisite for the progression of prostate cancer. Here, we analyzed clinical prostate cancer samples for the expression of receptors involved in cellular cholesterol uptake.

Methods: We screened mRNA microarray files of prostate cancer samples for alterations in the expression levels of cholesterol transporters. Furthermore, we performed immunohistochemistry analysis on human primary prostate cancer tissue sections derived from patients to investigate the correlation of SR-BI with clinicopathological parameters and the mTOR target pS6.

Results: In contrast to LDLR, we identified SR-BI mRNA and protein expression to be induced in high Gleason grade primary prostate cancers. Histologic analysis of prostate biopsies revealed that 53.6 % of all cancer samples and none of the non-cancer samples showed high SR-BI staining intensity. The disease-free survival time was reduced (P = 0.02) in patients expressing high intra-tumor levels of SR-BI. SR-BI mRNA correlated with HSD17B1 and HSD3B1 and SR-BI protein staining showed correlation with active ribosomal protein S6 (RS = 0.828, P < 0.00001).

Conclusions: We identified SR-BI to indicate human prostate cancer formation, suggesting that increased levels of SR-BI may be involved in the generation of a castration-resistant phenotype.

No MeSH data available.


Related in: MedlinePlus

Lipoprotein receptor expression patterns in prostate cancer (high grade and low grade). Histologic staining for LDLR and SR-BI in selected patients. Tissue derived from a 27-year-old patient diagnosed with prostate hyperplasia was stained for LDLR (a); a consecutive area of the same tumor was stained for SR-BI (b). Tissue derived from a 75-year-old patient diagnosed with prostate cancer T2N1M1c and Gleason score 5 + 4 was stained for LDLR (c); a consecutive area of the same tumor was stained for SR-BI (d). Tumor biopsies from a 72-year-old patient diagnosed with prostate cancer T2N0M0 and Gleason score 3 + 3 were analyzed for SR-BI expression (e and f). Black arrows indicate clusters of cells strongly positive for SR-BI. Kaplan Meier analysis of LDLR and SR-BI expression in GSE40272 (g–h). High LDLR expression had no effect on disease-free survival time (g). High SR-BI expression was associated with decreased disease-free survival time (h). Green = high expression (high), blue = low expression (low), DFS = disease-free survival time. P-values of the log-rank test are presented within each graph
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Fig3: Lipoprotein receptor expression patterns in prostate cancer (high grade and low grade). Histologic staining for LDLR and SR-BI in selected patients. Tissue derived from a 27-year-old patient diagnosed with prostate hyperplasia was stained for LDLR (a); a consecutive area of the same tumor was stained for SR-BI (b). Tissue derived from a 75-year-old patient diagnosed with prostate cancer T2N1M1c and Gleason score 5 + 4 was stained for LDLR (c); a consecutive area of the same tumor was stained for SR-BI (d). Tumor biopsies from a 72-year-old patient diagnosed with prostate cancer T2N0M0 and Gleason score 3 + 3 were analyzed for SR-BI expression (e and f). Black arrows indicate clusters of cells strongly positive for SR-BI. Kaplan Meier analysis of LDLR and SR-BI expression in GSE40272 (g–h). High LDLR expression had no effect on disease-free survival time (g). High SR-BI expression was associated with decreased disease-free survival time (h). Green = high expression (high), blue = low expression (low), DFS = disease-free survival time. P-values of the log-rank test are presented within each graph

Mentions: Because SR-BI expression showed an association with prostate cancer differentiation, we also tested for LDLR expression on selected sections with either low or high SR-BI staining intensity (Fig. 3a–d). Our case study showed that LDLR was constitutively expressed in prostate tissue, with lower expression levels in high-grade cancer samples. Interestingly, we also observed cases of low-grade prostate cancer, which displayed high SR-BI expression in a subpopulation of cells showing signs of tissue invasion (Fig. 3e and f). Cancer cells of this subpopulation either grew detached from the primary tumor, floating in the remaining glands (Fig. 3e), or separated from the solid tumor mass, infiltrating the surrounding tissue (Fig. 3f).Fig. 3


The HDL receptor SR-BI is associated with human prostate cancer progression and plays a possible role in establishing androgen independence.

Schörghofer D, Kinslechner K, Preitschopf A, Schütz B, Röhrl C, Hengstschläger M, Stangl H, Mikula M - Reprod. Biol. Endocrinol. (2015)

Lipoprotein receptor expression patterns in prostate cancer (high grade and low grade). Histologic staining for LDLR and SR-BI in selected patients. Tissue derived from a 27-year-old patient diagnosed with prostate hyperplasia was stained for LDLR (a); a consecutive area of the same tumor was stained for SR-BI (b). Tissue derived from a 75-year-old patient diagnosed with prostate cancer T2N1M1c and Gleason score 5 + 4 was stained for LDLR (c); a consecutive area of the same tumor was stained for SR-BI (d). Tumor biopsies from a 72-year-old patient diagnosed with prostate cancer T2N0M0 and Gleason score 3 + 3 were analyzed for SR-BI expression (e and f). Black arrows indicate clusters of cells strongly positive for SR-BI. Kaplan Meier analysis of LDLR and SR-BI expression in GSE40272 (g–h). High LDLR expression had no effect on disease-free survival time (g). High SR-BI expression was associated with decreased disease-free survival time (h). Green = high expression (high), blue = low expression (low), DFS = disease-free survival time. P-values of the log-rank test are presented within each graph
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4528807&req=5

Fig3: Lipoprotein receptor expression patterns in prostate cancer (high grade and low grade). Histologic staining for LDLR and SR-BI in selected patients. Tissue derived from a 27-year-old patient diagnosed with prostate hyperplasia was stained for LDLR (a); a consecutive area of the same tumor was stained for SR-BI (b). Tissue derived from a 75-year-old patient diagnosed with prostate cancer T2N1M1c and Gleason score 5 + 4 was stained for LDLR (c); a consecutive area of the same tumor was stained for SR-BI (d). Tumor biopsies from a 72-year-old patient diagnosed with prostate cancer T2N0M0 and Gleason score 3 + 3 were analyzed for SR-BI expression (e and f). Black arrows indicate clusters of cells strongly positive for SR-BI. Kaplan Meier analysis of LDLR and SR-BI expression in GSE40272 (g–h). High LDLR expression had no effect on disease-free survival time (g). High SR-BI expression was associated with decreased disease-free survival time (h). Green = high expression (high), blue = low expression (low), DFS = disease-free survival time. P-values of the log-rank test are presented within each graph
Mentions: Because SR-BI expression showed an association with prostate cancer differentiation, we also tested for LDLR expression on selected sections with either low or high SR-BI staining intensity (Fig. 3a–d). Our case study showed that LDLR was constitutively expressed in prostate tissue, with lower expression levels in high-grade cancer samples. Interestingly, we also observed cases of low-grade prostate cancer, which displayed high SR-BI expression in a subpopulation of cells showing signs of tissue invasion (Fig. 3e and f). Cancer cells of this subpopulation either grew detached from the primary tumor, floating in the remaining glands (Fig. 3e), or separated from the solid tumor mass, infiltrating the surrounding tissue (Fig. 3f).Fig. 3

Bottom Line: Recent data indicate that elevated cholesterol levels in the plasma are a prerequisite for the progression of prostate cancer.The disease-free survival time was reduced (P = 0.02) in patients expressing high intra-tumor levels of SR-BI.SR-BI mRNA correlated with HSD17B1 and HSD3B1 and SR-BI protein staining showed correlation with active ribosomal protein S6 (RS = 0.828, P < 0.00001).

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria. david.schoerghofer@meduniwien.ac.at.

ABSTRACT

Background: Human prostate cancer represents one of the most frequently diagnosed cancers in men worldwide. Currently, diagnostic methods are insufficient to identify patients at risk for aggressive prostate cancer, which is essential for early treatment. Recent data indicate that elevated cholesterol levels in the plasma are a prerequisite for the progression of prostate cancer. Here, we analyzed clinical prostate cancer samples for the expression of receptors involved in cellular cholesterol uptake.

Methods: We screened mRNA microarray files of prostate cancer samples for alterations in the expression levels of cholesterol transporters. Furthermore, we performed immunohistochemistry analysis on human primary prostate cancer tissue sections derived from patients to investigate the correlation of SR-BI with clinicopathological parameters and the mTOR target pS6.

Results: In contrast to LDLR, we identified SR-BI mRNA and protein expression to be induced in high Gleason grade primary prostate cancers. Histologic analysis of prostate biopsies revealed that 53.6 % of all cancer samples and none of the non-cancer samples showed high SR-BI staining intensity. The disease-free survival time was reduced (P = 0.02) in patients expressing high intra-tumor levels of SR-BI. SR-BI mRNA correlated with HSD17B1 and HSD3B1 and SR-BI protein staining showed correlation with active ribosomal protein S6 (RS = 0.828, P < 0.00001).

Conclusions: We identified SR-BI to indicate human prostate cancer formation, suggesting that increased levels of SR-BI may be involved in the generation of a castration-resistant phenotype.

No MeSH data available.


Related in: MedlinePlus