Altered expression of genes regulating angiogenesis in experimental androgen‐independent prostate cancer

Gustavsson, Heléne; Jennbacken, Karin; Welén, Karin; Damber, Jan‐Erik

doi:10.1002/pros.20672

Cited by 41 publications

(41 citation statements)

References 36 publications

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“…In localized PCa, VEGF-A expression patterns at the time of radical prostatectomy have been reported to correlate with risk of developing subsequent metastatic disease [14], suggestive of a prognostic role for VEGF-A expression. Furthermore, in advanced cancer, VEGF-A-dependent tumor-associated angiogenesis and progression has been proposed, based on the altered expression patterns for VEGF-A during the transition from the hormone-sensitive to castration-resistant state in cell lines [15], in vivo models and in the resected tissue of patients treated with hormonal therapy [16,17]. …”

Section: Discussionmentioning

confidence: 99%

An observational study of plasma vascular endothelial growth factors (VEGF) A and D expression in non-localized prostate cancer

Verdoorn

Feng

Ricke

et al. 2012

Journal of Men's Health

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Background The aim of the study was to measure plasma levels of the vascular endothelial growth factors (VEGF) A and D in serially collected blood specimens from non-localized prostate cancer (PCa) subjects. Methods Plasma VEGF A and D levels were measured in two serial specimens 3–6 months apart in two groups of non-localized stage PCa patients. Group 1 was comprised of patients with biochemical relapse after localized PCa treatments and/or patients with clinically metastatic hormone-sensitive stage PCa prior to receiving hormonal therapy. Group 2 included patients failing hormonal therapy for non-localized hormone-sensitive stage PCa. VEGF A and D levels were compared within each cancer group between the two time-points using the Wilcoxon Rank Sum test. Results At the first time-point in Group 1 (n = 46), median VEGF-A and D levels were measured at 5.2 (pg/ml) (range = 0–97) and 319 (range = 172–780) (pg/ml). For Group 2 (n = 34) VEGF-A level was 9.6 pg/ml (range = 0–78) and VEGF-D level was 377 pg/ml (range = 243–989) for the first measurement. Median time-period for the serial second specimen was 189 days in Group 1 and 84 days in Group 2. At the second time-point, in Group 1, VEGF-A levels were 0.0 pg/ml (P = 0.0002) while VEGF-D increased to 349 pg/ml (P = 0.002). For Group 2 patients at the second time-point, median VEGF-A was 0.0 pg/ml (P = 1.0) and VEGF-D was measured at 442 pg/ml (P = 0.008). Conclusions Higher plasma VEGF-D than VEGF-A expression in advanced PCa stages suggests a greater role for VEGF-D dependent lymph angiogenesis in advanced stage PCa, which needs further evaluation.

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Section: Discussionmentioning

confidence: 99%

An observational study of plasma vascular endothelial growth factors (VEGF) A and D expression in non-localized prostate cancer

Verdoorn

Feng

Ricke

et al. 2012

Journal of Men's Health

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“…ADAMTS-1 can cleave and remodel components of the extracellular matrix, and it has antiangiogenic properties. [29][30][31] Compared with normal hepatocytes, the expression of ADAMTS-1 was markedly decreased in PLC/PRF-5 cells. Furthermore, incubation with 10 lM 17-AAG resulted in a 1.88 (95% CI, 1.31-2.45)-fold increase in ADAMTS1 mRNA after 24 hours, confirming that 17-AAG can revert gene expression associated with vascular invasion.…”

Section: Itga7mentioning

confidence: 95%

Candidate therapeutic agents for hepatocellular cancer can be identified from phenotype‐associated gene expression signatures

Braconi

Meng

Swenson

et al. 2009

Cancer

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BACKGROUND: The presence of vascular invasion in hepatocellular cancer (HCC) correlates with prognosis, and is a critical determinant of both the therapeutic approach and the recurrence or intrahepatic metastases. The authors sought to identify candidate therapeutic agents capable of targeting the invasive phenotype in HCC. METHODS: A gene expression signature associated with vascular invasion derived from 81 human cases of HCC was used to screen a database of 453 genomic profiles associated with 164 bioactive molecules using the connectivity map. Candidate agents were identified by their inverse correlation to the query gene signature. The efficacy of the candidate agents to target invasion was experimentally verified in PLC/PRF‐5 and HepG2 HCC cells. RESULTS: The gene signature associated with vascular invasion in HCC comprised of 47 up‐regulated and 26 down‐regulated genes. Computational bioinformatics analysis revealed several putative candidates, including resveratrol and 17‐allylamino‐geldanamycin (17‐AAG). Both of these agents reduced HCC cell invasion at noncytotoxic concentrations. 17‐AAG, a heat shock protein 90 (HSP‐90) inhibitor, was shown to modulate the expression of several diverse cancer‐associated genes, including ADAMTS1, part of the query signature, and maspin, an HSP‐90–associated protein with a tumor suppressor role in HCC. CONCLUSIONS: Candidates for further evaluation as therapies to limit invasion in HCC have been identified using a computational bioinformatics analysis of phenotype‐associated gene expression. Phenotype targeting using genomic profiling is a rational approach for drug discovery. Therapeutic strategies targeting a defined cancer‐associated phenotype can be identified without a detailed knowledge of individual downstream targets. Cancer 2009. © 2009 American Cancer Society.

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“…LNCaP-19 was established in our laboratory as an in vitro derived castration-resistant subclone of LNCaP [23]. It has an increased angiogenic and invasive potential compared to its parental cell line [24, 25]. Compared to LNCaP, it also has metastatic potential [26, 27].…”

Section: Introductionmentioning

confidence: 99%

Osteoblasts stimulate the osteogenic and metastatic progression of castration-resistant prostate cancer in a novel model for in vitro and in vivo studies

Thulin

Jennbacken

Damber

et al. 2013

Clin Exp Metastasis

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Castration-resistant prostate cancer (CRPC) is strongly associated with sclerotic bone metastases and poor prognosis. Models that mimic human CRPC are needed to identify the mechanisms for prostate cancer (PC) growth in bone and to develop new therapeutic strategies. We characterize a new model, LNCaP-19, and investigate the interaction between tumor cells and osteoblasts in the sclerotic tumor response of CRPC. Osteogenic profiling of PC cell lines (LNCaP-19, LNCaP, C4-2B4, and PC-3) was performed by gene expression arrays and mineral staining. Conditioned medium from MC3T3-E1 was used for osteoblast stimulation of CRPC cells. The capacity of LNCaP-19 cells to induce sclerotic lesions was assessed in intratibial xenografts and verified by serum markers, histological analysis and bone mineral density (BMD) measurements. The CRPC cell line LNCaP-19 expresses a pronounced osteogenic profile compared to its parental androgen-dependent cell line LNCaP. Osteoblast-derived factors further increase the expression of genes known to enhance metastatic progression of PC. LNCaP-19 forms sclerotic tumors in tibia of castrated mice as evident by increased total BMD (P < 0.01). There was a strong correlation between serum osteocalcin and BMD (total: R2 0.811, P < 0.01, trabecular: R2 0.673, P < 0.05). For the first time we demonstrate that a CRPC cell line generated in vitro has osteogenic capacity and that osteomimicry can be an inherent feature of these cells. Osteoblast-derived factors further promote the osteogenic and metastatic phenotype in CRPC cells. Altogether, our model demonstrates that both tumor cells and osteoblasts are mediators of the bone forming process of CRPC.

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Altered expression of genes regulating angiogenesis in experimental androgen‐independent prostate cancer

Cited by 41 publications

References 36 publications

An observational study of plasma vascular endothelial growth factors (VEGF) A and D expression in non-localized prostate cancer

An observational study of plasma vascular endothelial growth factors (VEGF) A and D expression in non-localized prostate cancer

Candidate therapeutic agents for hepatocellular cancer can be identified from phenotype‐associated gene expression signatures

Osteoblasts stimulate the osteogenic and metastatic progression of castration-resistant prostate cancer in a novel model for in vitro and in vivo studies

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