Proangiogenic contribution of adiponectin toward mammary tumor growth in vivo

Shira Landskroner-Eiger, Binzhi Qian, Eric S. Muise, Andrea R. Nawrocki, Joel P. Berger, Eugene J. Fine, Wade Koba, Yingfeng Deng, Jeffrey W. Pollard, Philipp E. Scherer

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Purpose: Adipocytes represent one of the most abundant constituents of the mammary gland. They are essential for mammary tumor growth and survival. Metabolically, one of the more important fat-derived factors ("adipokines") is adiponectin (APN). Serum concentrations of APN negatively correlate with body mass index and insulin resistance. To explore the association of APN with breast cancer and tumor angiogenesis, we took an in vivo approach aiming to study its role in the mouse mammary tumor virus (MMTV)-polyoma middle T antigen (PyMT) mammary tumor model. Experimental Design: We compared the rates of tumor growth in MMTV-PyMT mice in wild-type and APN-null backgrounds. Results: Histology and micro-positron emission tomography imaging show that the rate of tumor growth is significantly reduced in the absence of APN at early stages. PyMT/APN knockout mice exhibit a reduction in their angiogenic profile resulting in nutrient deprivation of the tumors and tumor-associated cell death. Surprisingly, in more advanced malignant stages of the disease, tumor growth develops more aggressively in mice lacking APN, giving rise to a larger tumor burden, an increase in the mobilization of circulating endothelial progenitor cells, and a gene expression fingerprint indicative of more aggressive tumor cells. Conclusions: These observations highlight a novel important contribution of APN in mammary tumor development and angiogenesis, indicating that APN has potent angio-mimetic properties in tumor vascularization. However, in tumors deprived of APN, this antiangiogenic stress results in an adaptive response that fuels tumor growth through mobilization of circulating endothelial progenitor cells and the development of mechanisms enabling massive cell proliferation despite a chronically hypoxic microenvironment.

Original languageEnglish (US)
Pages (from-to)3265-3276
Number of pages12
JournalClinical Cancer Research
Volume15
Issue number10
DOIs
StatePublished - May 15 2009

Fingerprint

Adiponectin
Breast Neoplasms
Growth
Neoplasms
Viral Tumor Antigens
Mouse mammary tumor virus
Adipokines
Dermatoglyphics
Human Mammary Glands
Tumor Burden
Adipocytes
Knockout Mice
Positron-Emission Tomography
Insulin Resistance
Histology
Body Mass Index
Cell Death
Research Design
Fats
Cell Proliferation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Landskroner-Eiger, S., Qian, B., Muise, E. S., Nawrocki, A. R., Berger, J. P., Fine, E. J., ... Scherer, P. E. (2009). Proangiogenic contribution of adiponectin toward mammary tumor growth in vivo. Clinical Cancer Research, 15(10), 3265-3276. https://doi.org/10.1158/1078-0432.CCR-08-2649

Proangiogenic contribution of adiponectin toward mammary tumor growth in vivo. / Landskroner-Eiger, Shira; Qian, Binzhi; Muise, Eric S.; Nawrocki, Andrea R.; Berger, Joel P.; Fine, Eugene J.; Koba, Wade; Deng, Yingfeng; Pollard, Jeffrey W.; Scherer, Philipp E.

In: Clinical Cancer Research, Vol. 15, No. 10, 15.05.2009, p. 3265-3276.

Research output: Contribution to journalArticle

Landskroner-Eiger, S, Qian, B, Muise, ES, Nawrocki, AR, Berger, JP, Fine, EJ, Koba, W, Deng, Y, Pollard, JW & Scherer, PE 2009, 'Proangiogenic contribution of adiponectin toward mammary tumor growth in vivo', Clinical Cancer Research, vol. 15, no. 10, pp. 3265-3276. https://doi.org/10.1158/1078-0432.CCR-08-2649
Landskroner-Eiger S, Qian B, Muise ES, Nawrocki AR, Berger JP, Fine EJ et al. Proangiogenic contribution of adiponectin toward mammary tumor growth in vivo. Clinical Cancer Research. 2009 May 15;15(10):3265-3276. https://doi.org/10.1158/1078-0432.CCR-08-2649
Landskroner-Eiger, Shira ; Qian, Binzhi ; Muise, Eric S. ; Nawrocki, Andrea R. ; Berger, Joel P. ; Fine, Eugene J. ; Koba, Wade ; Deng, Yingfeng ; Pollard, Jeffrey W. ; Scherer, Philipp E. / Proangiogenic contribution of adiponectin toward mammary tumor growth in vivo. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 10. pp. 3265-3276.
@article{3201b5da4fef45a8b5c3b5f472c99507,
title = "Proangiogenic contribution of adiponectin toward mammary tumor growth in vivo",
abstract = "Purpose: Adipocytes represent one of the most abundant constituents of the mammary gland. They are essential for mammary tumor growth and survival. Metabolically, one of the more important fat-derived factors ({"}adipokines{"}) is adiponectin (APN). Serum concentrations of APN negatively correlate with body mass index and insulin resistance. To explore the association of APN with breast cancer and tumor angiogenesis, we took an in vivo approach aiming to study its role in the mouse mammary tumor virus (MMTV)-polyoma middle T antigen (PyMT) mammary tumor model. Experimental Design: We compared the rates of tumor growth in MMTV-PyMT mice in wild-type and APN-null backgrounds. Results: Histology and micro-positron emission tomography imaging show that the rate of tumor growth is significantly reduced in the absence of APN at early stages. PyMT/APN knockout mice exhibit a reduction in their angiogenic profile resulting in nutrient deprivation of the tumors and tumor-associated cell death. Surprisingly, in more advanced malignant stages of the disease, tumor growth develops more aggressively in mice lacking APN, giving rise to a larger tumor burden, an increase in the mobilization of circulating endothelial progenitor cells, and a gene expression fingerprint indicative of more aggressive tumor cells. Conclusions: These observations highlight a novel important contribution of APN in mammary tumor development and angiogenesis, indicating that APN has potent angio-mimetic properties in tumor vascularization. However, in tumors deprived of APN, this antiangiogenic stress results in an adaptive response that fuels tumor growth through mobilization of circulating endothelial progenitor cells and the development of mechanisms enabling massive cell proliferation despite a chronically hypoxic microenvironment.",
author = "Shira Landskroner-Eiger and Binzhi Qian and Muise, {Eric S.} and Nawrocki, {Andrea R.} and Berger, {Joel P.} and Fine, {Eugene J.} and Wade Koba and Yingfeng Deng and Pollard, {Jeffrey W.} and Scherer, {Philipp E.}",
year = "2009",
month = "5",
day = "15",
doi = "10.1158/1078-0432.CCR-08-2649",
language = "English (US)",
volume = "15",
pages = "3265--3276",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "10",

}

TY - JOUR

T1 - Proangiogenic contribution of adiponectin toward mammary tumor growth in vivo

AU - Landskroner-Eiger, Shira

AU - Qian, Binzhi

AU - Muise, Eric S.

AU - Nawrocki, Andrea R.

AU - Berger, Joel P.

AU - Fine, Eugene J.

AU - Koba, Wade

AU - Deng, Yingfeng

AU - Pollard, Jeffrey W.

AU - Scherer, Philipp E.

PY - 2009/5/15

Y1 - 2009/5/15

N2 - Purpose: Adipocytes represent one of the most abundant constituents of the mammary gland. They are essential for mammary tumor growth and survival. Metabolically, one of the more important fat-derived factors ("adipokines") is adiponectin (APN). Serum concentrations of APN negatively correlate with body mass index and insulin resistance. To explore the association of APN with breast cancer and tumor angiogenesis, we took an in vivo approach aiming to study its role in the mouse mammary tumor virus (MMTV)-polyoma middle T antigen (PyMT) mammary tumor model. Experimental Design: We compared the rates of tumor growth in MMTV-PyMT mice in wild-type and APN-null backgrounds. Results: Histology and micro-positron emission tomography imaging show that the rate of tumor growth is significantly reduced in the absence of APN at early stages. PyMT/APN knockout mice exhibit a reduction in their angiogenic profile resulting in nutrient deprivation of the tumors and tumor-associated cell death. Surprisingly, in more advanced malignant stages of the disease, tumor growth develops more aggressively in mice lacking APN, giving rise to a larger tumor burden, an increase in the mobilization of circulating endothelial progenitor cells, and a gene expression fingerprint indicative of more aggressive tumor cells. Conclusions: These observations highlight a novel important contribution of APN in mammary tumor development and angiogenesis, indicating that APN has potent angio-mimetic properties in tumor vascularization. However, in tumors deprived of APN, this antiangiogenic stress results in an adaptive response that fuels tumor growth through mobilization of circulating endothelial progenitor cells and the development of mechanisms enabling massive cell proliferation despite a chronically hypoxic microenvironment.

AB - Purpose: Adipocytes represent one of the most abundant constituents of the mammary gland. They are essential for mammary tumor growth and survival. Metabolically, one of the more important fat-derived factors ("adipokines") is adiponectin (APN). Serum concentrations of APN negatively correlate with body mass index and insulin resistance. To explore the association of APN with breast cancer and tumor angiogenesis, we took an in vivo approach aiming to study its role in the mouse mammary tumor virus (MMTV)-polyoma middle T antigen (PyMT) mammary tumor model. Experimental Design: We compared the rates of tumor growth in MMTV-PyMT mice in wild-type and APN-null backgrounds. Results: Histology and micro-positron emission tomography imaging show that the rate of tumor growth is significantly reduced in the absence of APN at early stages. PyMT/APN knockout mice exhibit a reduction in their angiogenic profile resulting in nutrient deprivation of the tumors and tumor-associated cell death. Surprisingly, in more advanced malignant stages of the disease, tumor growth develops more aggressively in mice lacking APN, giving rise to a larger tumor burden, an increase in the mobilization of circulating endothelial progenitor cells, and a gene expression fingerprint indicative of more aggressive tumor cells. Conclusions: These observations highlight a novel important contribution of APN in mammary tumor development and angiogenesis, indicating that APN has potent angio-mimetic properties in tumor vascularization. However, in tumors deprived of APN, this antiangiogenic stress results in an adaptive response that fuels tumor growth through mobilization of circulating endothelial progenitor cells and the development of mechanisms enabling massive cell proliferation despite a chronically hypoxic microenvironment.

UR - http://www.scopus.com/inward/record.url?scp=66149164443&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66149164443&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-08-2649

DO - 10.1158/1078-0432.CCR-08-2649

M3 - Article

VL - 15

SP - 3265

EP - 3276

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 10

ER -