Comparative Analysis of Metastasis Variants Derived from Human Prostate Carcinoma Cells

Conn, Erin M.; Bøtkjær, Kenneth A.; Kupriyanova, Tatyana A.; Andreasen, Peter A.; Deryugina, Elena I.; Quigley, James P.

doi:10.2353/ajpath.2009.090384

Cited by 45 publications

(43 citation statements)

References 62 publications

(71 reference statements)

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“…The chick embryo as a model to study tumour metastasis has been reported in a variety of cancer types including glioma [11], prostate [12], colorectal [13], renal [14], ovarian [15] and small-cell lung cancer [16]. In uveal melanoma, a small number of groups including our own have begun to examine the suitability of this model to monitor the growth and metastatic properties of uveal melanoma cells either grafted onto the CAM, injected intravenously or transplanted into the optic cup.…”

Section: The Chick Embryo Model In Cancer Biologymentioning

confidence: 99%

Use of the Chick Embryo Model in Uveal Melanoma

et al. 2015

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Animal models play a crucial role in basic and translational oncology research. Conventional rodent experiments, however, face ethical, practical and technical issues that limit their use. The chick embryo represents an accessible and economical in vivo model, which has long been used in developmental biology and for the study of angiogenesis. It is also a recognised xenograft model, and because of its lack of immune system in early development, the chick embryo has established itself as a key model system for cancer research, with which to study various steps in the metastatic process. In this chapter, we review the chick embryo model and the technical approaches adopted by cancer biologists, including advances in real-time imaging, and discuss how this has been or can be applied to improve our understanding of the biological events during uveal melanoma development and metastasis.

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Section: The Chick Embryo Model In Cancer Biologymentioning

confidence: 99%

Use of the Chick Embryo Model in Uveal Melanoma

et al. 2015

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“…HEK 293 cells stably transfected with CDCP1-WT or CDCP1-DM constructs are described in detail in Supplemental Information. The highly disseminating PC-hi/diss cells were selected from the prostate carcinoma PC-3 cell line as described (Conn et al , 2009). To knockdown CDCP1, the PC-hi/diss cells were stably transfected with pGIPZ1shCDCP1 vector along with the appropriate packaging vectors.…”

Section: Methodsmentioning

confidence: 99%

Blocking of CDCP1 cleavage in vivo prevents Akt-dependent survival and inhibits metastatic colonization through PARP1-mediated apoptosis of cancer cells

et al. 2011

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The CUB domain-containing protein 1 (CDCP1) is a transmembrane molecule that recently has been implicated in cancer progression. In this study we have established a novel mechanism for initiation of CDCP1-mediated signaling in vivo and demonstrated that specific 135→70 kDa processing of cell surface CDCP1 by extracellular serine proteases is a prerequisite for CDCP1-dependent survival of cancer cells during metastasis. The in vivo cleavage of CDCP1 triggers a survival program involving recruitment of Src and PKCδ, Src-mediated phosphorylation of cell surface-retained 70 kDa CDCP1, activation of Akt, and suppression of PARP1-induced apoptosis. We demonstrate in vivo that phosphorylated Src, PKCδ and Akt, all constitute activated elements of a CDCP1 signaling axis during tissue colonization of tumor cells. Preventing the in vivo cleavage of CDCP1 with unique anti-CDCP1 antibodies, serine protease inhibitors or genetic modulation of the cleavage site in the CDCP1 molecule completely abrogated survival signaling associated with the 70 kDa CDCP1 and induced PARP1 cleavage and PARP1-mediated apoptosis, ultimately resulting in substantial inhibition of tissue colonization by tumor cells. The lack of CDCP1 cleavage in the lung tissue of plasminogen knockout mice along with a coordinated reduction in tumor cell survival in a lung retention model and importantly the rescue of both by in vivo supplied plasmin, indicated that plasmin is the crucial serine protease executing in vivo cleavage of cell surface CDCP1 during early stages of lung colonization. Together, our findings indicate that in vivo blocking of CDCP1 cleavage upstream of CDCP1-induced pro-survival signaling provides a potential mechanism for therapeutic intervention into metastatic disease.

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“…Early studies suggested that NEPCa might secrete different kinds of cytokines and peptides, including bombesin, calcitonin, parathyroid hormone-related protein (PTHrP), serotonin and VEGF, to stimulate progression in its neighboring PCa (9–11, 31, 32). We first compared the expression of some cytokines and peptides related to p38/MAPK signals between LNCaP and NE1.3 cells (33–37).…”

Section: Resultsmentioning

confidence: 99%

“…The significance of NEPCa has been regarded as not only a sign for PCa progression, but also an inducer of growth and survival for the neighboring PCa by secreting a variety of cytokines and peptides (9–11, 31, 32). For example, NEPCa secrete several neuropeptides, including bombesin, which can act as a mitogen in PCa tumors via activation of the transcription factor Elk-1 and the immediate early gene c-fos (46).…”

Section: Discussionmentioning

confidence: 99%

“…Early studies suggested that NEPCa cells might secrete various factors, including bombesin, parathyroid hormone related protein (PTHrP), adrenomedullin and vascular endothelial growth factor (VEGF) to influence the surrounding PCa progression (9–11). However, the detailed mechanisms, especially their influences on the AR, the key factor for the PCa progression as well as their impact on the efficacy of chemotherapies such as Doc, remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Neuroendocrine prostate cancer (NEPCa) increased the neighboring PCa chemoresistance via altering the PTHrP/p38/Hsp27/androgen receptor (AR)/p21 signals

Chen

Sun

et al. 2016

Oncogene

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Prostatic neuroendocrine cells (NE) are an integral part of prostate cancer (PCa) that are associated with PCa progression. As the current androgen-deprivation therapy (ADT) with anti-androgens may promote the neuroendocrine PCa (NEPCa) development, and few therapies can effectively suppress NEPCa, understanding the impact of NEPCa on PCa progression may help us to develop better therapies to battle PCa. Here we found NEPCa cells could increase the docetaxel-resistance of their neighboring PCa cells. Mechanism dissection revealed that through secretion of PTHrP, NEPCa cells could alter the p38/MAPK/Hsp27 signals in their neighboring PCa cells that resulted in increased androgen receptor (AR) activity via promoting AR nuclear translocation. The consequences of increased AR function might then increase docetaxel-resistance via increasing p21 expression. In vivo xenograft mice experiments also confirmed NEPCa could increase the docetaxel-resistance of neighboring PCa, and targeting this newly identified PTHrP/p38/Hsp27/AR/p21 signaling pathway with either p38 inhibitor (SB203580) or sh-PTHrP may result in improving/restoring the docetaxel sensitivity to better suppress PCa.

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Comparative Analysis of Metastasis Variants Derived from Human Prostate Carcinoma Cells

Cited by 45 publications

References 62 publications

Use of the Chick Embryo Model in Uveal Melanoma

Use of the Chick Embryo Model in Uveal Melanoma

Blocking of CDCP1 cleavage in vivo prevents Akt-dependent survival and inhibits metastatic colonization through PARP1-mediated apoptosis of cancer cells

Neuroendocrine prostate cancer (NEPCa) increased the neighboring PCa chemoresistance via altering the PTHrP/p38/Hsp27/androgen receptor (AR)/p21 signals

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