Influence of the Kallikrein-Kinin System on Prostate and Breast Tumour Angiogenesis

Wright, Jaclyn K.; Botha, Julia; Naidoo, Strinivasen

doi:10.1159/000141918

Cited by 9 publications

(15 citation statements)

References 20 publications

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“…dMVECs and DU145 cells were cultured in endothelial basal medium (EBM-2) and Dulbecco's Modified Eagle's Medium (DMEM), respectively, as previously described 10 .…”

Section: Cell Culturementioning

confidence: 99%

“…They later suggested that BK enhanced angiogenesis by promoting tumour vascular permeability 16 . More recently TK, B1R and B2R have been shown to be present in the membrane projections of both endothelial and prostate cancer cells in vitro 10 .…”

Section: Introductionmentioning

confidence: 98%

“…The KKS has been implicated in angiogenesis, the growth of new blood vessels from the pre-existing vasculature 9,10 . Several studies have demonstrated a role for TK in neo-vascularisation following hind-limb ischemia in murine models [11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

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B1 but not B2 bradykinin receptor agonists promote DU145 prostate cancer cell proliferation and migration

Naidu¹,

Botha²,

Naidoo³

2014

Afr H. Sci.

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Background: The kallikrein-kinin system (KKS) is an endogenous pathway involved in angiogenesis and tumourigenesis, both vital for cancer growth and progression. Objectives: To investigate the effect of two bradykinin receptor (B1R and B2R) agonists on growth and motility of prostate tumour (DU145) and micro-vascular endothelial cells (dMVECs). Methods: Increasing concentrations of selective B1R and B2R agonists were added to cultured cells. Cell proliferation and migration were assessed using the 3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) and modified Boyden Chamber assays, respectively. Where significant stimulation was found, the influence of an antagonist was also investigated. Results: Neither growth nor motility of endothelial cells was affected by either agonist. In DU145 cells, while the B2R agonist was without any significant effect, the B1R agonist stimulated proliferation and migration at concentrations of 10nM and 50nM respectively. Further, this effect was abrogated when cells were pre-incubated with a B1R antagonist. Conclusions: Unlike the physiologically-active B2R, the pathologically-inducible B1R may be implicated in prostate tumourigenic events. The involvement of the KKS in malignant prostate pathology supports on-going exploration of bradykinin receptor antagonists as target candidates in the development of alternate approaches to cancer therapy.

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“…dMVECs and DU145 cells were cultured in endothelial basal medium (EBM-2) and Dulbecco's Modified Eagle's Medium (DMEM), respectively, as previously described 10 .…”

Section: Cell Culturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

B1 but not B2 bradykinin receptor agonists promote DU145 prostate cancer cell proliferation and migration

Naidu¹,

Botha²,

Naidoo³

2014

Afr H. Sci.

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“…Tumour medium was supplemented further as previously described. 11 Only DMVECs between passages 4 and 12 were used for the challenge and co-culture models.…”

Section: Cell Culturementioning

confidence: 99%

“…11 Briefly, DMVECs were seeded onto 8-chamber glass slides (Iwaki Glass Co., Iwaki, Japan) at 2 x 10 3 cells/cm 2 . After 24 h, MCF-7 cells were added to each DMVEC chamber at 2 x 10 3 cells/cm 2 .…”

Section: Co-culture Modelmentioning

confidence: 99%

The endothelin system in breast tumour–endothelial cell interactions

2011

Self Cite

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The role of endothelin-1 (ET-1) and its receptors (ET-RA and ET-RB) in tumour development and progression involves complex interactions. ET-1, produced by tumours and associated cells like endothelial cells, functions in an autocrine and paracrine manner to promote tumour angiogenesis. Thus, we hypothesised that endothelin, released into the tumour milieu by both tumours and the tumour vasculature, would influence angiogenesis. Therefore, this preliminary study aimed to investigate changes in ET1, ET-RA and ET-RB in breast tumour and microvascular endothelial cultures when each cell type was exposed directly to the other (co-culture model) as well as to the conditioned-medium metabolites of the other (challenge model). ET-1 secretion was measured by an enzyme-linked immunosorbent assay and ET-1, ET-RA and ET-RB expression investigated by the linked streptavidin-biotin method.In challenge experiments, endothelial metabolites significantly increased secretion of breast tumour ET-1. Tumour metabolites promoted endothelial membrane projections with no effect on ET-1 secretion. ET-1 and its receptors were immunolocalised in both cell types, including in projections. Increasing cancer cell conditioned medium resulted in decreased endothelial ET-RA and increased ET-RB staining. Co-cultures demonstrated ET proteins in projections of both cell types as well as at heterogeneous contact points. The findings support a role for the endothelin system in endothelial cell and breast cancer cell invasion. It is tempting to consider that early endothelial and tumour cell alterations may be promoted by ET-1 produced by both cell types. Further work is required that will examine localised cellular gene expression of the endothelin system as well as its pro-invasive and angiogenic effects in breast cancer models.

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Expression of thyroid-stimulating hormone receptors and thyroglobulin in limbic regions in the adult human brain

Naicker

Naidoo

2017

Metab Brain Dis

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Expression of the human thyroid-specific proteins, thyroid-stimulating hormone receptor (TSH-R) and thyroglobulin (TG) in non-thyroid tissue is well-documented. TSH-R has been identified in the heart, kidney, bone, pituitary, adipose tissue, skin and astrocyte cultures. TG has been identified in the skin, thymus and kidney. However, none of those previous studies had identified TSH-R or TG in specific human brain regions. Previously, a pilot study conducted by our group on normal adult human brain demonstrated TSH-R and TG in cortical neurons and cerebral vasculature, respectively, within various brain areas. In the present study, we extend this investigation of thyroid proteins specifically in limbic regions of normal human brain. Forensic human samples of amygdalae, cingulate gyrii, frontal cortices, hippocampii, hypothalamii, and thalamii were obtained from five individuals who had died of causes unrelated to head injury and had no evidence of brain disease or psychological abnormality. Tissues were probed with commercial polyclonal antibodies against human TSH-R and TG which resulted in the significant demonstration of neuronal TSH-R in all limbic regions examined. Other novel results demonstrated TG in vascular smooth muscle of all limbic regions and in some neurons. Finding thyroid proteins in limbic areas of the human brain is unique, and this study demonstrates that cerebro-limbic localisation of thyroid proteins may have potential roles in neuro-psycho-pharmacology.

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Influence of the Kallikrein-Kinin System on Prostate and Breast Tumour Angiogenesis

Cited by 9 publications

References 20 publications

B1 but not B2 bradykinin receptor agonists promote DU145 prostate cancer cell proliferation and migration

B1 but not B2 bradykinin receptor agonists promote DU145 prostate cancer cell proliferation and migration

The endothelin system in breast tumour–endothelial cell interactions

Expression of thyroid-stimulating hormone receptors and thyroglobulin in limbic regions in the adult human brain

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