Ornithine decarboxylase and extracellular polyamines regulate microvascular sprouting and actin cytoskeleton dynamics in endothelial cells.
(2010) In Experimental Cell Research 316. p.2683-2691- Abstract
- The polyamines are essential for cancer cell proliferation during tumorigenesis. Targeted inhibition of ornithine decarboxylase (ODC), i.e. a key enzyme of polyamine biosynthesis, by alpha-difluoromethylornithine (DFMO) has shown anti-neoplastic activity in various experimental models. This activity has mainly been attributed to the anti-proliferative effect of DFMO in cancer cells. Here, we provide evidence that unperturbed ODC activity is a requirement for proper microvessel sprouting ex vivo as well as the migration of primary human endothelial cells. DFMO-mediated ODC inhibition was reversed by extracellular polyamine supplementation, showing that anti-angiogenic effects of DFMO were specifically related to polyamine levels. ODC... (More)
- The polyamines are essential for cancer cell proliferation during tumorigenesis. Targeted inhibition of ornithine decarboxylase (ODC), i.e. a key enzyme of polyamine biosynthesis, by alpha-difluoromethylornithine (DFMO) has shown anti-neoplastic activity in various experimental models. This activity has mainly been attributed to the anti-proliferative effect of DFMO in cancer cells. Here, we provide evidence that unperturbed ODC activity is a requirement for proper microvessel sprouting ex vivo as well as the migration of primary human endothelial cells. DFMO-mediated ODC inhibition was reversed by extracellular polyamine supplementation, showing that anti-angiogenic effects of DFMO were specifically related to polyamine levels. ODC inhibition was associated with an abnormal morphology of the actin cytoskeleton during cell spreading and migration. Moreover, our data suggest that de-regulated actin cytoskeleton dynamics in DFMO treated endothelial cells may be related to constitutive activation of the small GTPase CDC42, i.e. a well-known regulator of cell motility and actin cytoskeleton remodeling. These insights into the potential role of polyamines in angiogenesis should stimulate further studies testing the combined anti-tumor effect of polyamine inhibition and established anti-angiogenic therapies in vivo. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1645325
- author
- Kucharzewska, Paulina LU ; Welch, Johanna LU ; Svensson, Katrin LU and Belting, Mattias LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Experimental Cell Research
- volume
- 316
- pages
- 2683 - 2691
- publisher
- Academic Press
- external identifiers
-
- wos:000281305800015
- pmid:20594968
- scopus:77955847340
- pmid:20594968
- ISSN
- 1090-2422
- DOI
- 10.1016/j.yexcr.2010.05.033
- language
- English
- LU publication?
- yes
- id
- 9273ee98-6900-4adb-9454-727398810b0d (old id 1645325)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/20594968?dopt=Abstract
- date added to LUP
- 2016-04-04 08:47:36
- date last changed
- 2022-01-29 03:59:08
@article{9273ee98-6900-4adb-9454-727398810b0d,
abstract = {{The polyamines are essential for cancer cell proliferation during tumorigenesis. Targeted inhibition of ornithine decarboxylase (ODC), i.e. a key enzyme of polyamine biosynthesis, by alpha-difluoromethylornithine (DFMO) has shown anti-neoplastic activity in various experimental models. This activity has mainly been attributed to the anti-proliferative effect of DFMO in cancer cells. Here, we provide evidence that unperturbed ODC activity is a requirement for proper microvessel sprouting ex vivo as well as the migration of primary human endothelial cells. DFMO-mediated ODC inhibition was reversed by extracellular polyamine supplementation, showing that anti-angiogenic effects of DFMO were specifically related to polyamine levels. ODC inhibition was associated with an abnormal morphology of the actin cytoskeleton during cell spreading and migration. Moreover, our data suggest that de-regulated actin cytoskeleton dynamics in DFMO treated endothelial cells may be related to constitutive activation of the small GTPase CDC42, i.e. a well-known regulator of cell motility and actin cytoskeleton remodeling. These insights into the potential role of polyamines in angiogenesis should stimulate further studies testing the combined anti-tumor effect of polyamine inhibition and established anti-angiogenic therapies in vivo.}},
author = {{Kucharzewska, Paulina and Welch, Johanna and Svensson, Katrin and Belting, Mattias}},
issn = {{1090-2422}},
language = {{eng}},
pages = {{2683--2691}},
publisher = {{Academic Press}},
series = {{Experimental Cell Research}},
title = {{Ornithine decarboxylase and extracellular polyamines regulate microvascular sprouting and actin cytoskeleton dynamics in endothelial cells.}},
url = {{http://dx.doi.org/10.1016/j.yexcr.2010.05.033}},
doi = {{10.1016/j.yexcr.2010.05.033}},
volume = {{316}},
year = {{2010}},
}