Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development

Veronika M. Metzler; Simone de Brot; Robert S. Robinson; Jennie N. Jeyapalan; Emad Rakha; Thomas Walton; David S. Gardner; Emma F. Lund; Jonathan Whitchurch; Daisy Haigh; Jack M. Lochray; Brian D. Robinson; Cinzia Allegrucci; Rupert G. Fray; Jenny L. Persson; Niels Ødum; Regina R. Miftakhova; Albert A. Rizvanov; Ieuan A. Hughes; Rieko Tadokoro-Cuccaro; David M. Heery; Catrin S. Rutland; Nigel P Mongan

doi:10.1016/j.placenta.2017.02.018

Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development

Veronika M. Metzler, Simone de Brot, Robert S. Robinson, Jennie N. Jeyapalan, Emad Rakha, Thomas Walton, David S. Gardner, Emma F. Lund, Jonathan Whitchurch, Daisy Haigh, Jack M. Lochray, Brian D. Robinson, Cinzia Allegrucci, Rupert G. Fray, Jenny L. Persson, Niels Ødum, Regina R. Miftakhova, Albert A. Rizvanov, Ieuan A. Hughes, Rieko Tadokoro-CuccaroDavid M. Heery, Catrin S. Rutland, Nigel P Mongan

6 Citations (Scopus)

Abstract

The placenta and tumors share important characteristics, including a requirement to establish effective angiogenesis. In the case of the placenta, optimal angiogenesis is required to sustain the blood flow required to maintain a successful pregnancy, whereas in tumors establishing new blood supplies is considered a key step in supporting metastases. Therefore the development of novel angiogenesis inhibitors has been an area of active research in oncology. A subset of the molecular processes regulating angiogenesis are well understood in the context of both early placentation and tumorigenesis. In this review we focus on the well-established role of androgen regulation of angiogenesis in cancer and relate these mechanisms to placental angiogenesis. The physiological actions of androgens are mediated by the androgen receptor (AR), a ligand dependent transcription factor. Androgens and the AR are essential for normal male embryonic development, puberty and lifelong health. Defects in androgen signalling are associated with a diverse range of clinical disorders in men and women including disorders of sex development (DSD), polycystic ovary syndrome in women and many cancers. We summarize the diverse molecular mechanisms of androgen regulation of angiogenesis and infer the potential significance of these pathways to normal and pathogenic placental function. Finally, we offer potential research applications of androgen-targeting molecules developed to treat cancer as investigative tools to help further delineate the role of androgen signalling in placental function and maternal and offspring health in animal models.

Original language	English
Journal	Placenta
Volume	56
Pages (from-to)	79-85
ISSN	0143-4004
DOIs	https://doi.org/10.1016/j.placenta.2017.02.018
Publication status	Published - Aug 2017

Keywords

Angiogenesis
Epigenetics
Nuclear receptor
VEGF

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.placenta.2017.02.018

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Metzler, V. M., de Brot, S., Robinson, R. S., Jeyapalan, J. N., Rakha, E., Walton, T., Gardner, D. S., Lund, E. F., Whitchurch, J., Haigh, D., Lochray, J. M., Robinson, B. D., Allegrucci, C., Fray, R. G., Persson, J. L., Ødum, N., Miftakhova, R. R., Rizvanov, A. A., Hughes, I. A., ... Mongan, N. P. (2017). Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development. Placenta, 56, 79-85. https://doi.org/10.1016/j.placenta.2017.02.018

Metzler, VM, de Brot, S, Robinson, RS, Jeyapalan, JN, Rakha, E, Walton, T, Gardner, DS, Lund, EF, Whitchurch, J, Haigh, D, Lochray, JM, Robinson, BD, Allegrucci, C, Fray, RG, Persson, JL, Ødum, N, Miftakhova, RR, Rizvanov, AA, Hughes, IA, Tadokoro-Cuccaro, R, Heery, DM, Rutland, CS & Mongan, NP 2017, 'Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development', Placenta, vol. 56, pp. 79-85. https://doi.org/10.1016/j.placenta.2017.02.018

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title = "Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development",

abstract = "The placenta and tumors share important characteristics, including a requirement to establish effective angiogenesis. In the case of the placenta, optimal angiogenesis is required to sustain the blood flow required to maintain a successful pregnancy, whereas in tumors establishing new blood supplies is considered a key step in supporting metastases. Therefore the development of novel angiogenesis inhibitors has been an area of active research in oncology. A subset of the molecular processes regulating angiogenesis are well understood in the context of both early placentation and tumorigenesis. In this review we focus on the well-established role of androgen regulation of angiogenesis in cancer and relate these mechanisms to placental angiogenesis. The physiological actions of androgens are mediated by the androgen receptor (AR), a ligand dependent transcription factor. Androgens and the AR are essential for normal male embryonic development, puberty and lifelong health. Defects in androgen signalling are associated with a diverse range of clinical disorders in men and women including disorders of sex development (DSD), polycystic ovary syndrome in women and many cancers. We summarize the diverse molecular mechanisms of androgen regulation of angiogenesis and infer the potential significance of these pathways to normal and pathogenic placental function. Finally, we offer potential research applications of androgen-targeting molecules developed to treat cancer as investigative tools to help further delineate the role of androgen signalling in placental function and maternal and offspring health in animal models.",

keywords = "Angiogenesis, Epigenetics, Nuclear receptor, VEGF",

author = "Metzler, {Veronika M.} and {de Brot}, Simone and Robinson, {Robert S.} and Jeyapalan, {Jennie N.} and Emad Rakha and Thomas Walton and Gardner, {David S.} and Lund, {Emma F.} and Jonathan Whitchurch and Daisy Haigh and Lochray, {Jack M.} and Robinson, {Brian D.} and Cinzia Allegrucci and Fray, {Rupert G.} and Persson, {Jenny L.} and Niels {\O}dum and Miftakhova, {Regina R.} and Rizvanov, {Albert A.} and Hughes, {Ieuan A.} and Rieko Tadokoro-Cuccaro and Heery, {David M.} and Rutland, {Catrin S.} and Mongan, {Nigel P}",

year = "2017",

month = aug,

doi = "10.1016/j.placenta.2017.02.018",

language = "English",

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journal = "Placenta",

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T1 - Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development

AU - Metzler, Veronika M.

AU - de Brot, Simone

AU - Robinson, Robert S.

AU - Jeyapalan, Jennie N.

AU - Rakha, Emad

AU - Walton, Thomas

AU - Gardner, David S.

AU - Lund, Emma F.

AU - Whitchurch, Jonathan

AU - Haigh, Daisy

AU - Lochray, Jack M.

AU - Robinson, Brian D.

AU - Allegrucci, Cinzia

AU - Fray, Rupert G.

AU - Persson, Jenny L.

AU - Ødum, Niels

AU - Miftakhova, Regina R.

AU - Rizvanov, Albert A.

AU - Hughes, Ieuan A.

AU - Tadokoro-Cuccaro, Rieko

AU - Heery, David M.

AU - Rutland, Catrin S.

AU - Mongan, Nigel P

PY - 2017/8

Y1 - 2017/8

N2 - The placenta and tumors share important characteristics, including a requirement to establish effective angiogenesis. In the case of the placenta, optimal angiogenesis is required to sustain the blood flow required to maintain a successful pregnancy, whereas in tumors establishing new blood supplies is considered a key step in supporting metastases. Therefore the development of novel angiogenesis inhibitors has been an area of active research in oncology. A subset of the molecular processes regulating angiogenesis are well understood in the context of both early placentation and tumorigenesis. In this review we focus on the well-established role of androgen regulation of angiogenesis in cancer and relate these mechanisms to placental angiogenesis. The physiological actions of androgens are mediated by the androgen receptor (AR), a ligand dependent transcription factor. Androgens and the AR are essential for normal male embryonic development, puberty and lifelong health. Defects in androgen signalling are associated with a diverse range of clinical disorders in men and women including disorders of sex development (DSD), polycystic ovary syndrome in women and many cancers. We summarize the diverse molecular mechanisms of androgen regulation of angiogenesis and infer the potential significance of these pathways to normal and pathogenic placental function. Finally, we offer potential research applications of androgen-targeting molecules developed to treat cancer as investigative tools to help further delineate the role of androgen signalling in placental function and maternal and offspring health in animal models.

AB - The placenta and tumors share important characteristics, including a requirement to establish effective angiogenesis. In the case of the placenta, optimal angiogenesis is required to sustain the blood flow required to maintain a successful pregnancy, whereas in tumors establishing new blood supplies is considered a key step in supporting metastases. Therefore the development of novel angiogenesis inhibitors has been an area of active research in oncology. A subset of the molecular processes regulating angiogenesis are well understood in the context of both early placentation and tumorigenesis. In this review we focus on the well-established role of androgen regulation of angiogenesis in cancer and relate these mechanisms to placental angiogenesis. The physiological actions of androgens are mediated by the androgen receptor (AR), a ligand dependent transcription factor. Androgens and the AR are essential for normal male embryonic development, puberty and lifelong health. Defects in androgen signalling are associated with a diverse range of clinical disorders in men and women including disorders of sex development (DSD), polycystic ovary syndrome in women and many cancers. We summarize the diverse molecular mechanisms of androgen regulation of angiogenesis and infer the potential significance of these pathways to normal and pathogenic placental function. Finally, we offer potential research applications of androgen-targeting molecules developed to treat cancer as investigative tools to help further delineate the role of androgen signalling in placental function and maternal and offspring health in animal models.

KW - Angiogenesis

KW - Epigenetics

KW - Nuclear receptor

KW - VEGF

U2 - 10.1016/j.placenta.2017.02.018

DO - 10.1016/j.placenta.2017.02.018

M3 - Journal article

C2 - 28238455

AN - SCOPUS:85013422177

SN - 0143-4004

VL - 56

SP - 79

EP - 85

JO - Placenta

JF - Placenta

ER -

Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development

Abstract

Keywords

UN SDGs

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