Sustained endothelial expression of HoxA5 in vivo impairs pathological angiogenesis and tumor progression

Ileana Cuevas, Hans Layman, Lisa Coussens, Nancy Boudreau

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

HoxA5 is expressed in quiescent endothelial cells (EC), but absent in activated angiogenic EC. To examine the efficacy of targeting HoxA5 therapeutically to quell pathologic or tumor angiogenesis, we generated an inducible, transgenic mouse model of sustained HoxA5 expression in ECs. During pathologic angiogenesis, sustained HoxA5 regulates expression several angiogenic effector molecules, notably increased expression of TSP-2 and reduced expression of VEGF, thus leading to inhibition of pathological angiogenesis in tissues. To evaluate if this impressive reduction of vascularization could also impact tumor angiogenesis, HoxA5 mice were bred with a mouse model of de novo squamous carcinogenesis, e.g., K14-HPV16 mice. Activation of EC-HoxA5 significantly reduced infiltration by mast cells into neoplastic skin, an early hallmark of progression to dysplasia, reduced angiogenic vasculature, and blunted characteristics of tumor progression. To evaluate HoxA5 as a therapeutic, topical application of a HoxA5 transgene onto early neoplastic skin of K14-HPV16 mice similarly resulted in a significant impairment of angiogenic vasculature and progression to dysplasia to a similar extent as observed with genetic delivery of HoxA5. Together these data indicate that HoxA5 represents a novel molecule for restricting pathological and tumorigenic angiogenesis.

Original languageEnglish (US)
Article numbere0121720
JournalPLoS One
Volume10
Issue number3
DOIs
StatePublished - Mar 30 2015

Fingerprint

Pathologic Neovascularization
Endothelial cells
angiogenesis
Tumors
neoplasms
Endothelial Cells
Skin
endothelial cells
Neoplasms
Molecules
skin (animal)
mice
Infiltration
Vascular Endothelial Growth Factor A
animal models
Chemical activation
Transgenes
Mast Cells
Tissue
Transgenic Mice

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Sustained endothelial expression of HoxA5 in vivo impairs pathological angiogenesis and tumor progression. / Cuevas, Ileana; Layman, Hans; Coussens, Lisa; Boudreau, Nancy.

In: PLoS One, Vol. 10, No. 3, e0121720, 30.03.2015.

Research output: Contribution to journalArticle

Cuevas, Ileana ; Layman, Hans ; Coussens, Lisa ; Boudreau, Nancy. / Sustained endothelial expression of HoxA5 in vivo impairs pathological angiogenesis and tumor progression. In: PLoS One. 2015 ; Vol. 10, No. 3.
@article{5f247bb38cdf41dea5f0c4b017b4b0ad,
title = "Sustained endothelial expression of HoxA5 in vivo impairs pathological angiogenesis and tumor progression",
abstract = "HoxA5 is expressed in quiescent endothelial cells (EC), but absent in activated angiogenic EC. To examine the efficacy of targeting HoxA5 therapeutically to quell pathologic or tumor angiogenesis, we generated an inducible, transgenic mouse model of sustained HoxA5 expression in ECs. During pathologic angiogenesis, sustained HoxA5 regulates expression several angiogenic effector molecules, notably increased expression of TSP-2 and reduced expression of VEGF, thus leading to inhibition of pathological angiogenesis in tissues. To evaluate if this impressive reduction of vascularization could also impact tumor angiogenesis, HoxA5 mice were bred with a mouse model of de novo squamous carcinogenesis, e.g., K14-HPV16 mice. Activation of EC-HoxA5 significantly reduced infiltration by mast cells into neoplastic skin, an early hallmark of progression to dysplasia, reduced angiogenic vasculature, and blunted characteristics of tumor progression. To evaluate HoxA5 as a therapeutic, topical application of a HoxA5 transgene onto early neoplastic skin of K14-HPV16 mice similarly resulted in a significant impairment of angiogenic vasculature and progression to dysplasia to a similar extent as observed with genetic delivery of HoxA5. Together these data indicate that HoxA5 represents a novel molecule for restricting pathological and tumorigenic angiogenesis.",
author = "Ileana Cuevas and Hans Layman and Lisa Coussens and Nancy Boudreau",
year = "2015",
month = "3",
day = "30",
doi = "10.1371/journal.pone.0121720",
language = "English (US)",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Sustained endothelial expression of HoxA5 in vivo impairs pathological angiogenesis and tumor progression

AU - Cuevas, Ileana

AU - Layman, Hans

AU - Coussens, Lisa

AU - Boudreau, Nancy

PY - 2015/3/30

Y1 - 2015/3/30

N2 - HoxA5 is expressed in quiescent endothelial cells (EC), but absent in activated angiogenic EC. To examine the efficacy of targeting HoxA5 therapeutically to quell pathologic or tumor angiogenesis, we generated an inducible, transgenic mouse model of sustained HoxA5 expression in ECs. During pathologic angiogenesis, sustained HoxA5 regulates expression several angiogenic effector molecules, notably increased expression of TSP-2 and reduced expression of VEGF, thus leading to inhibition of pathological angiogenesis in tissues. To evaluate if this impressive reduction of vascularization could also impact tumor angiogenesis, HoxA5 mice were bred with a mouse model of de novo squamous carcinogenesis, e.g., K14-HPV16 mice. Activation of EC-HoxA5 significantly reduced infiltration by mast cells into neoplastic skin, an early hallmark of progression to dysplasia, reduced angiogenic vasculature, and blunted characteristics of tumor progression. To evaluate HoxA5 as a therapeutic, topical application of a HoxA5 transgene onto early neoplastic skin of K14-HPV16 mice similarly resulted in a significant impairment of angiogenic vasculature and progression to dysplasia to a similar extent as observed with genetic delivery of HoxA5. Together these data indicate that HoxA5 represents a novel molecule for restricting pathological and tumorigenic angiogenesis.

AB - HoxA5 is expressed in quiescent endothelial cells (EC), but absent in activated angiogenic EC. To examine the efficacy of targeting HoxA5 therapeutically to quell pathologic or tumor angiogenesis, we generated an inducible, transgenic mouse model of sustained HoxA5 expression in ECs. During pathologic angiogenesis, sustained HoxA5 regulates expression several angiogenic effector molecules, notably increased expression of TSP-2 and reduced expression of VEGF, thus leading to inhibition of pathological angiogenesis in tissues. To evaluate if this impressive reduction of vascularization could also impact tumor angiogenesis, HoxA5 mice were bred with a mouse model of de novo squamous carcinogenesis, e.g., K14-HPV16 mice. Activation of EC-HoxA5 significantly reduced infiltration by mast cells into neoplastic skin, an early hallmark of progression to dysplasia, reduced angiogenic vasculature, and blunted characteristics of tumor progression. To evaluate HoxA5 as a therapeutic, topical application of a HoxA5 transgene onto early neoplastic skin of K14-HPV16 mice similarly resulted in a significant impairment of angiogenic vasculature and progression to dysplasia to a similar extent as observed with genetic delivery of HoxA5. Together these data indicate that HoxA5 represents a novel molecule for restricting pathological and tumorigenic angiogenesis.

UR - http://www.scopus.com/inward/record.url?scp=84926443254&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84926443254&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0121720

DO - 10.1371/journal.pone.0121720

M3 - Article

C2 - 25821967

AN - SCOPUS:84926443254

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 3

M1 - e0121720

ER -