Endocrine/paracrine/autocrine survival factor activity of bone microenvironment participates in the development of androgen ablation and chemotherapy refractoriness of prostate cancer metastasis in skeleton.

Bogdanos, John; Karamanolakis, Dimitrios; Τέντα, Ρωξάνη; Tsintavis, A; Milathianakis, Constantine; Mitsiades, Constantine S.; Koutsilieris, Michael

doi:10.1677/erc.0.0100279

Cited by 61 publications

(42 citation statements)

References 56 publications

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“…Neither the 15dPGJ2 (2 μM) nor the rosiglitazone (10 μM) produced apoptosis of PC-3 cells, after treatment for 24 h, 48 h, 72 h, and 96 h ( Figure 1C,D). Contrary to this, 100 nM of adriamycin did produce clear evidence of apoptosis of PC-3 cells, confirming our previously published data ( Figure 3B) (11,(13)(14)(15)(16)18,19,31). Combination treatment using adriamycin (100 nM) plus rosiglitazone (10 μM) further increased the rate of apoptosis of PC-3 cells, as compared with adriamycin monotherapy ( Figure 3D).…”

Section: Combination Treatments Of Pparγ Ligands With Adriamycinsupporting

confidence: 90%

“…The blastic nature of bone metastasis in prostate cancer involves the role of several bone metastasis microenvironment-related growth substances, such as insulin-like growth factor 1 (IGF-1), interleukin 6 (IL-6), parathyroid hormone-related peptide (PTHrP), transforming growth factor β 1 (TGFβ1), and endothelin 1 (ET-1) (3)(4)(5)(6)(7)(8)(9)(10)(11)(12), which are involved, at least in part, in the development of the androgen ablation refractoriness and chemotherapy resistant phenotype of patients with advanced prostate cancer (13)(14)(15)(16)(17)(18)(19). Recently, the PPARγ expression in several malignant tumors has been well documented while the exogenous administration of PPARγ ligands has produced anticancer actions, in vitro (20).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Combination Treatments Of Pparγ Ligands With Adriamycinsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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

Papageorgiou

Pitulis

Manoussakis

et al. 2008

Mol Med

View full text Add to dashboard Cite

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“…17 Similarly, it has been shown that TGFb1, IL-1, and IL-8 induce changes that may be related to androgen independence. 14,18,19 Furthermore, we identified a thought-provoking correlation between race and anemia. In a multivariate analysis, African-American race alone was not a strong predictor of death or disease progression.…”

Section: Discussionmentioning

confidence: 86%

The prognostic value of hemoglobin change after initiating androgen‐deprivation therapy for newly diagnosed metastatic prostate cancer

Beer

Tangen

Bland

et al. 2006

Cancer

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BACKGROUND. The objective of this study was to characterize changes in hemoglobin (HGB) levels after the initiation of androgen‐deprivation therapy (ADT) in patients with previously untreated, metastatic prostate cancer who were enrolled in a large clinical trial. METHODS. The multivariate associations between 3‐month change in HGB and baseline characteristics were evaluated with a linear regression model. The associations between 3‐month change in HGB level and time‐to‐event outcomes, including overall survival and progression‐free survival, were evaluated by using proportional hazards regression models. RESULTS. Quartiles of baseline HGB levels were ≤12.0 g/dL, from 12.1 to 13.7 g/dL, from 13.8 to 14.7 g/dL, and >14.7 g/dL. Overall, 3 months after initiating ADT, the mean HGB level declined 0.54 g/dL (standard deviation [SD], 1.68 g/dL); however, the mean HGB level increased by 0.99 g/dL (SD, 1.83 g/dL) in patients who had baseline HGB levels <12 g/dL and decreased 1.04 g/dL (SD, 1.28 g/dL) in patients who had baseline HGB levels ≥12 g/dL. After adjusting for potential confounders, including baseline HGB level, a decline in HGB after 3 months of ADT was associated independently with shorter survival (hazards ratio [HR], 1.10 per 1 g/dL decline; P = .0035) and shorter progression‐free survival (HR, 1.08 per 1 g/dL decline; P = .013). An unexpected finding was that the effect of baseline HGB on overall and progression‐free survival varied significantly by race. CONCLUSIONS. In a sample of men with newly diagnosed, metastatic prostate cancer, a decline in HGB level after 3 months of ADT was associated with shorter survival and progression‐free survival after adjusting for disease status and other baseline covariates. Although race alone was not a strong predictor of death or disease progression, the effect of the baseline HGB level on overall and progression‐free survival varied significantly by race. Cancer 2006. © 2006 American Cancer Society.

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“…The latter is composed of an IR hemi-receptor linked to an IGF-IR hemi-receptor and has been reported to have an important role in cancer biology (29)(30)(31). Recently, the two IR isoforms (IR-A and IR-B) have been reported that are overexpressed in cancer tissues (32), whereas the expression of IGF-1R has been previously characterized in KLE cells in our laboratory (7).…”

Section: Discussionmentioning

confidence: 99%

Insulinlike Growth Factor-1Ec (MGF) Expression in Eutopic and Ectopic Endometrium: Characterization of the MGF E-Peptide Actions In Vitro

Milingos

Philippou

Armakolas

et al. 2010

Mol Med

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The transcription of the insulinlike growth factor 1 (igf-1) gene generates three mRNA isoforms, namely IGF-1Ea, IGF-1Eb and IGF1Ec (or MGF [mechano growth factor]). Herein, we analyzed the expression of IGF-1 isoforms in eutopic and ectopic endometrium (red lesions and endometriotic cysts) of women with endometriosis, and we characterized the actions of a synthetic MGF E-peptide on KLE cells. Our data documented that all three igf-1 gene transcripts are expressed in the stromal cells of the eutopic and ectopic endometrium; however, endometriotic cysts contained significantly lower IGF-1 isoform expression, both at the mRNA and protein level, as was shown using semiquantitative PCR and immunohistochemical methods. In addition, the glandular cells of the eutopic endometrium did not express any of the IGF-1 isoforms; however, the glandular cells of the ectopic endometrium (red lesions) did express the IGF-1Ec at mRNA and protein level. Furthermore, synthetic MGF E-peptide, which comprised the last 24 amino acids of the MGF, stimulated the growth of the KLE cells. Experimental silencing of the type 1 IGF receptor (IGF-1R) and insulin receptor expression of KLE cells (siRNA knock-out methods) did not alter the mitogenic action of the synthetic MGF E-peptide, revealing that MGF E-peptide stimulates the growth of KLE cells via an IGF-1R-independent and insulin receptor-independent mechanism. These data suggest that the IGF-1Ec transcript might generate, apart from mature IGF-1 peptide, another posttranslational bioactive product that may have an important role in endometriosis pathophysiology.

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Endocrine/paracrine/autocrine survival factor activity of bone microenvironment participates in the development of androgen ablation and chemotherapy refractoriness of prostate cancer metastasis in skeleton.

Cited by 61 publications

References 56 publications

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

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

The prognostic value of hemoglobin change after initiating androgen‐deprivation therapy for newly diagnosed metastatic prostate cancer

Insulinlike Growth Factor-1Ec (MGF) Expression in Eutopic and Ectopic Endometrium: Characterization of the MGF E-Peptide Actions In Vitro

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