Prognostic significance of epithelial/stromal caveolin‐1 expression in prostatic hyperplasia, high grade prostatic intraepithelial hyperplasia and prostatic carcinoma and its correlation with microvessel density

Mohammed, Dareen A.; Helal, Duaa S

doi:10.1016/j.jnci.2017.01.002

Cited by 16 publications

(13 citation statements)

References 22 publications

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“…The results from Mohammed, D.A. [ 24 ] also suggest that the expression of caveolin-1 in prostate cancer is significantly higher than in BPH and high-grade PIN, indicating that caveolin-1 plays an important role in the occurrence and metastasis of prostate cancer and is not related to the invasion of prostate cancer. Caveolin-1 expression is upregulated in the terminal development stages of various tumors and in various stages of urinary tumors, and it increases with tumor malignancy.…”

Section: Discussionmentioning

confidence: 99%

Expression and clinical significance of Caveolin-1 in prostate Cancer after transurethral surgery

2018

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BackgroundProstate cancer is a common malignancy of the male genitourinary system that occurs worldwide. The current research aims to investigate caveolin-1 expression in prostate cancer tissue and its relationship with pathological grade, clinical pathologic staging, and preoperative prostate-specific antigen (PSA) levels.MethodsFrom January 2012 to December 2014, samples from 47 patients with prostate cancer who had received transurethral prostatic resection (TURP) and 20 patients with benign prostatic hyperplasia were collected at the First Affiliated Hospital of Guangxi Medical University. Caveolin-1 was detected by streptavidin-perosidase (SP) immunohistochemical staining in pathological tissue slices. The results were statistically analyzed for pathological grade, clinical stage, and preoperative PSA level.ResultsThe expression of caveolin-1 was significantly higher in prostate cancer samples than in benign prostatic hyperplasia samples (P < 0.05), and caveolin-1 expression was significantly different among the pathological grades of poorly, moderately and well-differentiated prostate cancer (P < 0.05). The difference in caveolin-1 expression was significant for different clinical stages (T1-T2 and T3-T4) of prostate cancer (P < 0.05). The difference in caveolin-1 expression was not significant among samples with different preoperative PSA levels (0–10, 10–100 and > 100 μg/L) (P > 0.05).ConclusionsCaveolin-1 is closely related to the pathological grade and clinical stage of prostate cancer after transurethral surgery, and it may be a novel tumor marker for prostate cancer. The expression of caveolin-1 is not associated with preoperative serum PSA levels.

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Section: Discussionmentioning

confidence: 99%

Expression and clinical significance of Caveolin-1 in prostate Cancer after transurethral surgery

2018

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“…In fact, suppression of caveolin‐1 expression induces androgen sensitivity in hormone refractory and metastatic prostate cancer cells in a mouse model system. In further support, caveolin‐1 is also known to regulate hormonal independence through lipid synthesis and abnormal signaling of the androgen receptor . The secretion of LEVs and their cargo content are topics of intense investigation in several cancer systems.…”

Section: Discussionmentioning

confidence: 99%

“…In further support, caveolin-1 is also known to regulate hormonal independence through lipid synthesis and abnormal signaling of the androgen receptor. [70][71][72][73] The secretion of LEVs and their cargo content are topics of intense investigation in several cancer systems. Our finding that the oxidoreductase enzyme NQO2 piggybacking on caveolin-1 and released extracellularly in LEVs adds a potentially therapeutic significance for the overall role for oxidoreductases in the modulation of the TME and in the establishment and maintenance of bone metastases in prostate cancer.…”

Section: Figurementioning

confidence: 99%

NRH:quinone oxidoreductase 2 (NQO2) and glutaminase (GLS) both play a role in large extracellular vesicles (LEV) formation in preclinical LNCaP‐C4‐2B prostate cancer model of progressive metastasis

et al. 2018

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In the course of studies aimed at the role of oxidative stress in the development of metastatic potential in the LNCaP-C4-2B prostate cancer progression model system, we found a relative decrease in the level of expression of the cytoplasmic nicotinamide riboside: quinone oxidoreductase (NQO2) and an increase in the oxidative stress in C4-2B cells compared to that in LNCaP or its derivatives C4 and C4-2. It was also found that C4-2B cells specifically shed large extracellular vesicles (LEVs) suggesting that these LEVs and their cargo could participate in the establishment of the osseous metastases. The level of expression of caveolin-1 increased as the system progresses from LNCaP to C4-2B. Since NQO2 RNA levels were not changed in LNCaP, C4, C4-2, and C4-2B, we tested an altered cellular distribution hypothesis of NQO2 being compartmentalized in the membrane fractions of C4-2B cells which are rich in lipid rafts and caveolae. This was confirmed when the detergent resistant membrane fractions were probed on immunoblots. Moreover, when the LEVs were analyzed for membrane associated caveolin-1 as possible cargo, we noticed that the enzyme NQO2 was also a component of the cargo along with caveolin-1 as seen in double immunofluorescence studies. Molecular modeling studies showed that a caveolin-1 accessible site is present in NQO2. Specific interaction between NQO2 and caveolin-1 was confirmed using deletion constructs of caveolin-1 fused with glutathione S-transferase (GST). Interestingly, whole cell lysate and mitochondrial preparations of LNCaP, C4, C4-2, and C4-2B showed an increasing expression of glutaminase (GLS, kidney type). The extrusion of LEVs appears to be a specific property of the bone metastatic C4-2B cells and this process could be inhibited by a GLS specific inhibitor BPTES, suggesting the critical role of a functioning glutamine metabolism. Our results indicate that a high level of expression of caveolin-1 in C4-2B cells contributes to an interaction between caveolin-1 and NQO2 and to their packaging as cargo in the shed LEVs. These results suggest an important role of membrane associated oxidoreductases in the establishment of osseous metastases in prostate cancer.

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“…Tissue vascularization has usually been described following three different quantitative methods (subjective, objective non-morphometric and morphometric methods), based on the detection of the differential staining of the vessels with more or less specific techniques (immunohistochemistry against factor VIII related von Willebrand factor [ 28 ], CD34 [ 29 ], CD31 [ 15 ], caveolin [ 30 ] or CD105 [ 31 ] for blood vessels; against D2-40 [ 32 ], PROX1 [ 10 ] and LYVE-1 [ 5 ] for lymphatic vessels and traditional histology methods such as the combination of H&E and Victoria blue-Van Gieson stainings, to reliably distinguish lymphatic channels from small blood vessels [ 33 ]) on whole slides and/or in TMAs slides. When evaluating microvascularization by subjective vascular grading, the number of microvessels is assessed manually with a microscope in the most active regions of vascularization (hot-spots), in small fields.…”

Section: Discussionmentioning

confidence: 99%

Lymph microvascularization as a prognostic indicator in neuroblastoma

et al. 2018

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Neuroblastoma is the most common extra-cranial solid pediatric cancer and causes approximately 15% of all childhood deaths from cancer. Although lymphatic vasculature is a prerequisite for the maintenance of tissue fluid balance and immunity in the body, little is known about the relationship between lymphatic vascularization and prognosis in neuroblastoma. We used our previously-published custom-designed tool to close open-outline vessels and measure the density, size and shape of all lymphatic vessels and microvascular segments in 332 primary neuroblastoma contained in tissue microarrays. The results were correlated with clinical and biological features of known prognostic value and with risk of progression to establish histological lymphatic vascular patterns associated with unfavorable histology. A high proportion of irregular intermediate lymphatic capillaries and irregular small collector vessels were present in tumors from patients with metastatic stage, undifferentiating neuroblasts and/or classified in the high risk. In addition, a higher lymphatic microvascularization density was found to be predictive of overall survival. Our findings show the crucial role of lymphatic vascularization in metastatic development and maintenance of tumor tissue homeostasis. These patterns may therefore help to indicate more accurate pre-treatment risk stratification and could provide candidate targets for novel therapies.

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Prognostic significance of epithelial/stromal caveolin‐1 expression in prostatic hyperplasia, high grade prostatic intraepithelial hyperplasia and prostatic carcinoma and its correlation with microvessel density

Cited by 16 publications

References 22 publications

Expression and clinical significance of Caveolin-1 in prostate Cancer after transurethral surgery

Expression and clinical significance of Caveolin-1 in prostate Cancer after transurethral surgery

NRH:quinone oxidoreductase 2 (NQO2) and glutaminase (GLS) both play a role in large extracellular vesicles (LEV) formation in preclinical LNCaP‐C4‐2B prostate cancer model of progressive metastasis

Lymph microvascularization as a prognostic indicator in neuroblastoma

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