Abstract
The molecular signature that defines tumor microvasculature will likely provide dues as to how vascular-dependent tumor proliferation is regulated. Using purified endothelial cells, we generated a database of gene expression changes accompanying vascular proliferation in invasive breast cancer. In contrast to normal mammary vasculature, invasive breast cancer vasculature expresses extracellular matrix and surface proteins characteristic of proliferating and migrating endothelial cells. We define and validate the up-regulated expression of VE-cadherin and osteonectin in breast tumor vasculature. In contrast to other tumor types, invasive breast cancer vasculature induced a high expression level of specific transcription factors, including SNAIL1 and HEYL, that may drive gene expression changes necessary for breast tumor neovascularization. We demonstrate the expression of HEYL in tumor endothelial cells and additionally establish the ability of HEYL to both induce proliferation and attenuate programmed cell death of primary endothelial cells in vitro. We also establish that an additional intracellular protein and previously defined metastasis-associated gene, PRL3, appears to be expressed predominately in the vasculature of invasive breast cancers and is able to enhance the migration of endothelial cells in vitro. Together, our results provide unique insights into vascular regulation in breast tumors and suggest specific roles for genes in driving tumor angiogenesis.
| Original language | English |
|---|---|
| Pages (from-to) | 7857-7866 |
| Number of pages | 10 |
| Journal | Cancer Research |
| Volume | 64 |
| Issue number | 21 |
| DOIs | |
| Publication status | Published - Nov 1 2004 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Alterations in vascular gene expression in invasive breast carcinoma. / Parker, Belinda S.; Argani, Pedram; Cook, Brian P.; Liangfeng, Han; Chartrand, Scott D.; Zhang, Mindy; Saha, Saurabh; Bardelli, Alberto; Jiang, Yide; St. Martin, Thia B.; Nacht, Mariana; Teicher, Beverly A.; Klinger, Katherine W.; Sukumar, Saraswati; Madden, Stephen L.
In: Cancer Research, Vol. 64, No. 21, 01.11.2004, p. 7857-7866.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Alterations in vascular gene expression in invasive breast carcinoma
AU - Parker, Belinda S.
AU - Argani, Pedram
AU - Cook, Brian P.
AU - Liangfeng, Han
AU - Chartrand, Scott D.
AU - Zhang, Mindy
AU - Saha, Saurabh
AU - Bardelli, Alberto
AU - Jiang, Yide
AU - St. Martin, Thia B.
AU - Nacht, Mariana
AU - Teicher, Beverly A.
AU - Klinger, Katherine W.
AU - Sukumar, Saraswati
AU - Madden, Stephen L.
PY - 2004/11/1
Y1 - 2004/11/1
N2 - The molecular signature that defines tumor microvasculature will likely provide dues as to how vascular-dependent tumor proliferation is regulated. Using purified endothelial cells, we generated a database of gene expression changes accompanying vascular proliferation in invasive breast cancer. In contrast to normal mammary vasculature, invasive breast cancer vasculature expresses extracellular matrix and surface proteins characteristic of proliferating and migrating endothelial cells. We define and validate the up-regulated expression of VE-cadherin and osteonectin in breast tumor vasculature. In contrast to other tumor types, invasive breast cancer vasculature induced a high expression level of specific transcription factors, including SNAIL1 and HEYL, that may drive gene expression changes necessary for breast tumor neovascularization. We demonstrate the expression of HEYL in tumor endothelial cells and additionally establish the ability of HEYL to both induce proliferation and attenuate programmed cell death of primary endothelial cells in vitro. We also establish that an additional intracellular protein and previously defined metastasis-associated gene, PRL3, appears to be expressed predominately in the vasculature of invasive breast cancers and is able to enhance the migration of endothelial cells in vitro. Together, our results provide unique insights into vascular regulation in breast tumors and suggest specific roles for genes in driving tumor angiogenesis.
AB - The molecular signature that defines tumor microvasculature will likely provide dues as to how vascular-dependent tumor proliferation is regulated. Using purified endothelial cells, we generated a database of gene expression changes accompanying vascular proliferation in invasive breast cancer. In contrast to normal mammary vasculature, invasive breast cancer vasculature expresses extracellular matrix and surface proteins characteristic of proliferating and migrating endothelial cells. We define and validate the up-regulated expression of VE-cadherin and osteonectin in breast tumor vasculature. In contrast to other tumor types, invasive breast cancer vasculature induced a high expression level of specific transcription factors, including SNAIL1 and HEYL, that may drive gene expression changes necessary for breast tumor neovascularization. We demonstrate the expression of HEYL in tumor endothelial cells and additionally establish the ability of HEYL to both induce proliferation and attenuate programmed cell death of primary endothelial cells in vitro. We also establish that an additional intracellular protein and previously defined metastasis-associated gene, PRL3, appears to be expressed predominately in the vasculature of invasive breast cancers and is able to enhance the migration of endothelial cells in vitro. Together, our results provide unique insights into vascular regulation in breast tumors and suggest specific roles for genes in driving tumor angiogenesis.
UR - http://www.scopus.com/inward/record.url?scp=7444251118&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=7444251118&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-04-1976
DO - 10.1158/0008-5472.CAN-04-1976
M3 - Article
C2 - 15520192
AN - SCOPUS:7444251118
VL - 64
SP - 7857
EP - 7866
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 21
ER -