Tumour metabolites regulate tissue kallikrein in human umbilical vein endothelial cells

S. Naidoo, D. Raidoo, R. Mahabeer, M. McLean

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)
8 Downloads (Pure)

Abstract

Angiogenesis, the sprouting of new blood vessels, is tightly mediated via a myriad of endogenous factors. A pro-angiogenic alteration facilitates the formation of neovascular tumour networks, thereby providing mechanisms for uncontrolled growth. The kallikrein-kinin system is postulated to be pro-angiogenic since its components have been detected in both endothelial cells and tumour tissue. No studies have, however, focussed on the role of tissue kallikrein (TK) in human angiogenic endothelial cell-tumour interactions. This study has optimised a challenge model whereby endothelial cells are presented with neuroblastoma metabolites, and vice versa. Image analysis of immunoreactive TK revealed a dose-dependant, significant reduction of TK localisation within endothelial cells, while gene expression remained unchanged, the latter determined by in situ RT-PCR. Neuroblastoma cells, when challenged with endothelial cell metabolites, displayed no change in TK synthesis or localisation. Alterations in TK synthesis and/or storage by angiogenic endothelial cells may be mediated by tumour-released signals and possibly indicate a shift from a proteolytic to a mitogenic function of TK. The challenge model provides a relatively simple experimental system to study angiogenic factors in tumour-endothelial cell interaction, and is the first to localise both TK and its mRNA within angiogenic endothelial and tumour cells.

Original languageEnglish
Pages (from-to)117-127
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1691
Issue number2-3
DOIs
Publication statusPublished - 3 May 2004
Externally publishedYes

Fingerprint

Tissue Kallikreins
Human Umbilical Vein Endothelial Cells
Endothelial Cells
Neoplasms
Neuroblastoma
Cell Communication
Kallikrein-Kinin System
Angiogenesis Inducing Agents
Blood Vessels
Gene Expression
Polymerase Chain Reaction
Messenger RNA

Cite this

@article{eb5c9d6d7cd8406b900dabe5437e3fd3,
title = "Tumour metabolites regulate tissue kallikrein in human umbilical vein endothelial cells",
abstract = "Angiogenesis, the sprouting of new blood vessels, is tightly mediated via a myriad of endogenous factors. A pro-angiogenic alteration facilitates the formation of neovascular tumour networks, thereby providing mechanisms for uncontrolled growth. The kallikrein-kinin system is postulated to be pro-angiogenic since its components have been detected in both endothelial cells and tumour tissue. No studies have, however, focussed on the role of tissue kallikrein (TK) in human angiogenic endothelial cell-tumour interactions. This study has optimised a challenge model whereby endothelial cells are presented with neuroblastoma metabolites, and vice versa. Image analysis of immunoreactive TK revealed a dose-dependant, significant reduction of TK localisation within endothelial cells, while gene expression remained unchanged, the latter determined by in situ RT-PCR. Neuroblastoma cells, when challenged with endothelial cell metabolites, displayed no change in TK synthesis or localisation. Alterations in TK synthesis and/or storage by angiogenic endothelial cells may be mediated by tumour-released signals and possibly indicate a shift from a proteolytic to a mitogenic function of TK. The challenge model provides a relatively simple experimental system to study angiogenic factors in tumour-endothelial cell interaction, and is the first to localise both TK and its mRNA within angiogenic endothelial and tumour cells.",
author = "S. Naidoo and D. Raidoo and R. Mahabeer and M. McLean",
year = "2004",
month = "5",
day = "3",
doi = "10.1016/j.bbamcr.2003.12.007",
language = "English",
volume = "1691",
pages = "117--127",
journal = "Biochimica et Biophysica Acta - Molecular Cell Research",
issn = "0167-4889",
publisher = "Elsevier",
number = "2-3",

}

Tumour metabolites regulate tissue kallikrein in human umbilical vein endothelial cells. / Naidoo, S.; Raidoo, D.; Mahabeer, R.; McLean, M.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1691, No. 2-3, 03.05.2004, p. 117-127.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Tumour metabolites regulate tissue kallikrein in human umbilical vein endothelial cells

AU - Naidoo, S.

AU - Raidoo, D.

AU - Mahabeer, R.

AU - McLean, M.

PY - 2004/5/3

Y1 - 2004/5/3

N2 - Angiogenesis, the sprouting of new blood vessels, is tightly mediated via a myriad of endogenous factors. A pro-angiogenic alteration facilitates the formation of neovascular tumour networks, thereby providing mechanisms for uncontrolled growth. The kallikrein-kinin system is postulated to be pro-angiogenic since its components have been detected in both endothelial cells and tumour tissue. No studies have, however, focussed on the role of tissue kallikrein (TK) in human angiogenic endothelial cell-tumour interactions. This study has optimised a challenge model whereby endothelial cells are presented with neuroblastoma metabolites, and vice versa. Image analysis of immunoreactive TK revealed a dose-dependant, significant reduction of TK localisation within endothelial cells, while gene expression remained unchanged, the latter determined by in situ RT-PCR. Neuroblastoma cells, when challenged with endothelial cell metabolites, displayed no change in TK synthesis or localisation. Alterations in TK synthesis and/or storage by angiogenic endothelial cells may be mediated by tumour-released signals and possibly indicate a shift from a proteolytic to a mitogenic function of TK. The challenge model provides a relatively simple experimental system to study angiogenic factors in tumour-endothelial cell interaction, and is the first to localise both TK and its mRNA within angiogenic endothelial and tumour cells.

AB - Angiogenesis, the sprouting of new blood vessels, is tightly mediated via a myriad of endogenous factors. A pro-angiogenic alteration facilitates the formation of neovascular tumour networks, thereby providing mechanisms for uncontrolled growth. The kallikrein-kinin system is postulated to be pro-angiogenic since its components have been detected in both endothelial cells and tumour tissue. No studies have, however, focussed on the role of tissue kallikrein (TK) in human angiogenic endothelial cell-tumour interactions. This study has optimised a challenge model whereby endothelial cells are presented with neuroblastoma metabolites, and vice versa. Image analysis of immunoreactive TK revealed a dose-dependant, significant reduction of TK localisation within endothelial cells, while gene expression remained unchanged, the latter determined by in situ RT-PCR. Neuroblastoma cells, when challenged with endothelial cell metabolites, displayed no change in TK synthesis or localisation. Alterations in TK synthesis and/or storage by angiogenic endothelial cells may be mediated by tumour-released signals and possibly indicate a shift from a proteolytic to a mitogenic function of TK. The challenge model provides a relatively simple experimental system to study angiogenic factors in tumour-endothelial cell interaction, and is the first to localise both TK and its mRNA within angiogenic endothelial and tumour cells.

UR - http://www.scopus.com/inward/record.url?scp=1942508890&partnerID=8YFLogxK

U2 - 10.1016/j.bbamcr.2003.12.007

DO - 10.1016/j.bbamcr.2003.12.007

M3 - Article

VL - 1691

SP - 117

EP - 127

JO - Biochimica et Biophysica Acta - Molecular Cell Research

JF - Biochimica et Biophysica Acta - Molecular Cell Research

SN - 0167-4889

IS - 2-3

ER -