The relation of androgen receptors status, neuroendocrine differentiation and angiogenesis to biochemical failure after radical prostatectomy for localized prostate cancer

Revelos, Kyriakos; Petraki, Constantina; Vaslamatzis, Michael; Papanastassiou, P.; Mastoris, C.; Argyrakos, Theodoros; Alevizopoulos, Nektarios; Vrionis, E.; Koutsilieris, M.

doi:10.1200/jco.2004.22.90140.4691

Cited by 8 publications

(9 citation statements)

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“…As a predictor of prognosis, greater microvessel density has been associated with an increased likelihood of biochemical failure after prostatectomy [18][19][20] and worse cancer-specific survival. 11,21 However, other studies have found that microvessel density is not an independent predictor of prostate cancer outcomes after adjusting for Gleason grade.…”

Section: 17mentioning

confidence: 99%

Prospective Study of Prostate Tumor Angiogenesis and Cancer-Specific Mortality in the Health Professionals Follow-Up Study

Mucci

Powolny

Giovannucci

et al. 2009

JCO

121

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A B S T R A C T PurposeTumor growth requires the development of independent vascular networks that are often primitive in morphology and function. We examined whether microvessel morphology contributes to the considerable biologic heterogeneity of prostate cancer. MethodsWe evaluated microvessel morphology as a predictor of prostate cancer mortality among 572 men in the Health Professionals Follow-Up Study diagnosed with cancer during 1986 to 2000. We immunostained prostatectomy tumor block sections for endothelial marker CD34 and assessed microvessel density, vessel size (area and diameter), and irregularity of vessel lumen using image analysis. Proportional hazards models were used to assess microvessel density and morphology in relation to lethal prostate cancer. ResultsPoorly differentiated tumors exhibited greater microvessel density, greater irregularity of the vessel lumen, and smaller vessels. During 20 years of follow-up, 44 men developed bone metastases or died of cancer. Men with tumors exhibiting the smallest vessel diameter, based on quartiles, were 6.0 times more likely (95% CI, 1.8 to 20.0) to develop lethal prostate cancer. Men with the most irregularly shaped vessels were 17.1 times more likely (95% CI, 2.3 to 128) to develop lethal disease. Adjusting for Gleason grade and prostate-specific antigen levels did not qualitatively change the results. Microvessel density was not linked to cancer-specific mortality after adjusting for clinical factors. ConclusionAggressive tumors form vessels that are primitive in morphology and function, with consequences for metastases. Vascular size and irregularity reflect the angiogenic potential of prostate cancer and may serve as biomarkers to predict prostate cancer mortality several years after diagnosis.

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Section: 17mentioning

confidence: 99%

Prospective Study of Prostate Tumor Angiogenesis and Cancer-Specific Mortality in the Health Professionals Follow-Up Study

Mucci

Powolny

Giovannucci

et al. 2009

JCO

121

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“…Inhibitors of proteins in several PI3K/ AKT signaling pathways recently have entered clinical trials. These include inhibitors that target both upstream regulators of PI3K/AKT, such as growth factor receptors, and downstream effectors, such as the components of the mTOR pathway (17,(40)(41)(42)(43).…”

Section: Discussionmentioning

confidence: 99%

“…Previously, we have shown that exogenous administration of IGF-1 protects PC-3 cells from adriamycininduced apoptosis. Indeed, a combination therapy using dexamethasone (suppressing the urokinase type plasminogen activator [uPA]-mediated increase of IGF-1 production in bone metastasis) and somatostatin analog (suppressing the systemic GH-dependent liver-derived IGF-1 production) has produced objective clinical responses to androgen ablation refractory prostate cancer patients (28)(29)(30)(31)42,43,52). Therefore, the concept of a novel hormonal manipulation focusing on the neutralization of the survival factor activity of local and systemic inhibitors of the apoptosis of prostate cancer cells has been proposed for patients with stage D3 prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Rosiglitazone Attenuates Insulin-Like Growth Factor 1 Receptor Survival Signaling in PC-3 Cells

Papageorgiou

Pitulis

Manoussakis

et al. 2008

Mol Med

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PPARγ, a member of the peroxisome proliferator-activated receptor family, is overexpressed in prostate cancer. Natural and synthetic ligands of PPARγ via genomic and nongenomic actions promote cell cycle arrest and apoptosis of several prostate cancer cells, in vitro. Insulin-like growth factor 1 (IGF-1) inhibits the adriamycin-induced apoptosis of PC-3 human prostate cancer cells. Therefore, we have analyzed the ability of two PPARγ ligands,15dPGJ2 and rosiglitazone, a natural and a synthetic PPARγ ligand, respectively, to increase the adriamycin-induced cytotoxicity of PC-3 cells and to suppress the IGF-1 survival effect on adriamycin-induced apoptosis of PC-3 cells. Our data revealed that both the PPARγ ligands increased the adriamycin-induced cytostasis of PC-3 cells, however, only rosiglitazone added to the adriamycin-induced apoptosis of PC-3 cells. In addition, rosiglitazone attenuated the type I IGF receptor (IGF-1R) survival signaling on adriamycin-induced apoptosis of PC-3 cells via its nongenomic action on ERK1/2 and AKT phosphorylation. Because the IGF-1R signaling is probably the most important host tissue (bone) metastasis microenvironment-related survival signaling for prostate cancer cells, we conclude that rosiglitazone effects on IGF-1R-mediated activation of ERK1/2 and AKT could have clinical implications for the management of androgen ablationrefractory and chemotherapy-resistant advanced prostate cancer with bone metastasis.

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“…Notably, recent studies have shown that BM-EPCs are recruited to the angiogenic switch in tumor growth and metastatic progression (4,13,14) and blood levels of EPCs tend to increase in cancer patients and correlate with the stage of the malignant disease (15). In prostate cancer, although microvessel density is related to clinical stage, progression, metastasis and survival (16)(17)(18), it is not known whether EPCs contribute to the bone metastasis of PCa. The mobilization, homing and incorporation of EPCs into tumors are multi-step and multi-factor events during tumor vasculogenesis.…”

Section: Hypoxia Of Pc-3 Prostate Cancer Cells Enhances Migration Andmentioning

confidence: 99%

Hypoxia of PC-3 prostate cancer cells enhances migration and vasculogenesis in vitro of bone marrow-derived endothelial progenitor cells by secretion of cytokines

et al. 2013

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Abstract. Hypoxia is a key inducer of neovascularization which is essential for tumor growth, invasion and metastasis. It has been proposed that the recruitment of bone-marrowderived endothelial progenitor cells (BM-EPCs) is pivotal and requires the participation of several tumor-derived cytokines. However, it is not known whether prostate cancer (PCa) cells contribute to the recruitment and vasculogenesis of EPCs in PCa progression. In the present study, we demonstrated that all conditioned medium (CM) of PC-3 PCa cells promoted proliferation and migration, and augmented the vasculogenesis capacity of BM-EPCs, and 24-h hypoxia (24H)-CM presented stronger ability compared to 24-h normoxia (24N)-CM and 48H-CM. Human cytokine antibody array with 174 anticytokine antibodies revealed the changes of cytokine in CMs. Twenty-five types of cytokines significantly increased in 24H-CM compared with 24N-CM. Eleven types of cytokines (5 factors increased and 6 decreased) were significantly different between 48H-CM and 48N-CM. Twelve types of cytokines (4 factors increased and 8 decreased) were significantly different between 48H-CM and 24H-CM. Furthermore, according to the Gene Ontology analysis, all altered cytokines were involved in proliferation, chemotaxis, cell motility, cell migration, vasculogenesis and angiogenesis. Of note, the changed regularity of cytokines in the 24H-CM and 48H-CM of PC-3 cells was in concert with the functional changes of BM-EPCs treated by different CM of PC-3 cells in enhancing the proliferation, migration and vasculogenesis potential of BM-EPCs. These findings suggest that PCa cells may have the potential to modulate their microenvironment and facilitate BM-EPC migration and vasculogenesis by secretion of cytokines in the early stage of hypoxia.

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The relation of androgen receptors status, neuroendocrine differentiation and angiogenesis to biochemical failure after radical prostatectomy for localized prostate cancer

Cited by 8 publications

References 0 publications

Prospective Study of Prostate Tumor Angiogenesis and Cancer-Specific Mortality in the Health Professionals Follow-Up Study

Prospective Study of Prostate Tumor Angiogenesis and Cancer-Specific Mortality in the Health Professionals Follow-Up Study

Rosiglitazone Attenuates Insulin-Like Growth Factor 1 Receptor Survival Signaling in PC-3 Cells

Hypoxia of PC-3 prostate cancer cells enhances migration and vasculogenesis in vitro of bone marrow-derived endothelial progenitor cells by secretion of cytokines

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