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Proangiogenic Contribution of Adiponectin toward Mammary Tumor Growth In vivo
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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.
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“Using a genetic approach, our laboratory identified that adiponectin has potent angiomimetic properties in tumor vascularization (75).”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [75]
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“Adiponectin, for example, has been shown to induce angiogenesis in hypoxic fat pads and tumors (75,91)”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [75]
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Cites
Tumor Angiogenesis and Metastasis — Correlation in Invasive Breast Carcinoma
Weidner, N., Semple, J. P., Welch, W. R., & Folkman, J. (1991) · New England Journal of Medicine · doi:10.1056/nejm199101033240101 · Cited by 5,598
Why Do Cancers Have High Aerobic Glycolysis?
Gatenby, R. A., & Gillies, R. J. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1478 · Cited by 4,784
Orimo, A., Gupta, P. B., Sgroi, D. C., Arenzana-Seisdedos, F., Delaunay, T., Naeem, R., Carey, V. J., Richardson, A. L., & Weinberg, R. A. (2005) · Cell · doi:10.1016/j.cell.2005.02.034 · Cited by 3,759
A Novel Serum Protein Similar to C1q, Produced Exclusively in Adipocytes
Scherer, P. E., Williams, S. P., Fogliano, M., Baldini, G., & Lodish, H. F. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.45.26746 · Cited by 3,238
Self-citationModes of resistance to anti-angiogenic therapy
Bergers, G., & Hanahan, D. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2442 · Cited by 2,953 · cited 5×
“Antiangiogenic treatment can cause recruitment of various bone marrow–derived cells that have the capacity to fuel tumor growth (26, 28, 38).”
BackgroundInfluentialThe adipocyte-secreted protein Acrp30 enhances hepatic insulin action
Berg, A. H., Combs, T. P., Du, X., Brownlee, M., & Scherer, P. E. (2001) · Nature Medicine · doi:10.1038/90992 · Cited by 2,526
Self-citationAdipocytes as regulators of energy balance and glucose homeostasis
Rosen, E. D., & Spiegelman, B. M. (2006) · Nature · doi:10.1038/nature05483 · Cited by 2,170 · cited 1×
“The physiologic role of adipose tissue as a dynamic organ has shown its crucial role in maintaining normal systemic energy balance, glucose homeostasis, and the immune response (1, 2).”
BackgroundDiet-induced insulin resistance in mice lacking adiponectin/ACRP30
Maeda, N., Shimomura, I., Kishida, K., Nishizawa, H., Matsuda, M., Nagaretani, H., Furuyama, N., Kondo, H., Takahashi, M., Arita, Y., et al. (2002) · Nature Medicine · doi:10.1038/nm724 · Cited by 2,114
Lyden, D., Hattori, K., Dias, S., Costa, C., Blaikie, P., Butros, L., Chadburn, A., Heissig, B., Marks, W., Witte, L., et al. (2001) · Nature Medicine · doi:10.1038/nm1101-1194 · Cited by 1,860
Asahara, T., Takahashi, T., Masuda, H., Kalka, C., Chen, D., Iwaguro, H., Inai, Y., Silver, M., & Isner, J. M. (1999) · The EMBO Journal · doi:10.1093/emboj/18.14.3964 · Cited by 1,851
Batchelor, T. T., Sorensen, A. G., di Tomaso, E., Zhang, W.-T., Duda, D. G., Cohen, K. S., Kozak, K. R., Cahill, D. P., Chen, P.-J., Zhu, M., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2006.11.021 · Cited by 1,769
Guy, C. T., Cardiff, R., & Muller, W. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.3.954-961.1992 · Cited by 1,710
Guy, C. T., Cardiff, R. D., & Muller, W. J. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.3.954 · Cited by 1,523
Obesity-associated improvements in metabolic profile through expansion of adipose tissue
Kim, J.-Y., van de Wall, E., Laplante, M., Azzara, A., Trujillo, M. E., Hofmann, S. M., Schraw, T., Durand, J. L., Li, H., Li, G., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31021 · Cited by 1,310 · cited 3×
“Despite the massive hyperplasia of the fat pads in these mice overexpressing APN, the fat pads remain minimally inflamed and fully insulin sensitive and do not display the classic hallmarks of expansion under suboptimal conditions, such as hypoxia and macrophage infiltration (29).”
BackgroundInfluentialSelf-citationExpression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer
Hughes, T. R., Mao, M., Jones, A. R., Burchard, J., Marton, M. J., Shannon, K. W., Lefkowitz, S. M., Ziman, M., Schelter, J. M., Meyer, M. R., et al. (2001) · Nature Biotechnology · doi:10.1038/86730 · Cited by 1,298
PPARγ: a Nuclear Regulator of Metabolism, Differentiation, and Cell Growth
Rosen, E. D., & Spiegelman, B. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.r100034200 · Cited by 1,178
Du, R., Lu, K. V., Petritsch, C. K., Liu, P., Ganß, R., Passegue, E. A., Song, H., VandenBerg, S. R., Johnson, R. S., Werb, Z., et al. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.01.034 · Cited by 1,166
Advances in Male Contraception
Page, S. T., Amory, J. K., & Bremner, W. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0041 · Cited by 1,138
Lin, E. Y., Jones, J. G., Li, P., Zhu, L., Whitney, K. D., Muller, W. J., & Pollard, J. W. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63568-7 · Cited by 1,109
Self-citationScherer, P. E. (2006) · Diabetes · doi:10.2337/db06-0263 · Cited by 1,092
Self-citationMacrophages Regulate the Angiogenic Switch in a Mouse Model of Breast Cancer
Lin, E. Y., Li, J.-F., Gnatovskiy, L., Deng, Y., Zhu, L., Grzesik, D. A., Qian, H., Xue, X.-N., & Pollard, J. W. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1278 · Cited by 1,074
Self-citationShibata, R., Sato, K., Pimentel, D. R., Takemura, Y., Kihara, S., Ohashi, K., Funahashi, T., Ouchi, N., & Walsh, K. (2005) · Nature Medicine · doi:10.1038/nm1295 · Cited by 982
Endogenous glucose production is inhibited by the adipose-derived protein Acrp30
Combs, T. P., Berg, A. H., Obici, S., Scherer, P. E., & Rossetti, L. (2001) · Journal of Clinical Investigation · doi:10.1172/jci14120 · Cited by 955
Self-citationAdiponectin – journey from an adipocyte secretory protein to biomarker of the metabolic syndrome
TRUJILLO, M. E., & Scherer, P. E. (2005) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01426.x · Cited by 782
Self-citationOuchi, N., Kobayashi, H., Kihara, S., Kumada, M., Sato, K., Inoue, T., Funahashi, T., & Walsh, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310389200 · Cited by 759 · cited 2×
“Previous work has proposed a role for APN in vessel remodeling and promotion of angiogenesis in an in vivo hind limb model of ischemia (25, 37).”
BackgroundA microenvironmental model of carcinogenesis
Gatenby, R. A., & Gillies, R. J. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2255 · Cited by 741
Bråkenhielm, E., Veitonmäki, N., Cao, R., Kihara, S., Matsuzawa, Y., Zhivotovsky, B., Funahashi, T., & Cao, Y. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308671100 · Cited by 736
Hattori, K., Dias, S., Heissig, B., Hackett, N. R., Lyden, D. C., Tateno, M., Hicklin, D. J., Zhu, Z., Witte, L., Crystal, R. G., et al. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.9.1005 · Cited by 688
Selective Suppression of Endothelial Cell Apoptosis by the High Molecular Weight Form of Adiponectin
Kobayashi, H., Ouchi, N., Kihara, S., Walsh, K. X., Kumada, M., Abe, Y., Funahashi, T., & Matsuzawa, Y. (2004) · Circulation Research · doi:10.1161/01.res.0000119921.86460.37 · Cited by 666
Nawrocki, A. R., Rajala, M. W., Tomás, E., Pajvani, U. B., Saha, A. K., Trumbauer, M. E., Pang, Z., Chen, A. S., Ruderman, N. B., Chen, H., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505311200 · Cited by 655
Self-citationAdipose Tissue-Derived Factors: Impact on Health and Disease
Trujillo, M. E., & Scherer, P. E. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0033 · Cited by 624
Self-citationThe multifaceted circulating endothelial cell in cancer: towards marker and target identification
Bertolini, F., Shaked, Y., Mancuso, P., & Kerbel, R. S. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1971 · Cited by 586
Peroxisome-proliferator-activated receptors and cancers: complex stories
Michalik, L., Desvergne, B., & Wahli, W. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1254 · Cited by 576
Combs, T. P., Wagner, J. A., Berger, J. P., Doebber, T. W., Wang, W., Zhang, B. B., Tanen, M., Berg, A. H., O’Rahilly, S., Savage, D. B., et al. (2002) · Endocrinology · doi:10.1210/endo.143.3.8662 · Cited by 568
Self-citationAdiponectin and Breast Cancer Risk
Mantzoros, C. S., Petridou, E. T., Dessypris, N., Chavelas, C., Dalamaga, Μ., Alexe, D. M., Papadiamantis, Y., Markopoulos, C. J., Spanos, E., Chrousos, G. P., et al. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031804 · Cited by 532
Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis
Stockmann, C., Doedens, A. L., Weidemann, A., Zhang, N., Takeda, N., Greenberg, J. I., Cheresh, D. A., & Johnson, R. S. (2008) · Nature · doi:10.1038/nature07445 · Cited by 489
Murine Models to Evaluate Novel and Conventional Therapeutic Strategies for Cancer
Talmadge, J. E., Singh, R. K., Fidler, I. J., & Raz, A. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.060929 · Cited by 486
Molecular links between obesity and breast cancer
Lorincz, A., & Sukumar, S. V. (2006) · Endocrine Related Cancer · doi:10.1677/erc.1.00729 · Cited by 447
Shaked, Y., Henke, E., Roodhart, J. M. L., Mancuso, P., Langenberg, M. H. G., Colleoni, M. A., Daenen, L. G. M., Man, S., Xu, P., Emmenegger, U., et al. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.08.001 · Cited by 439
Iyengar, P., Espina, V. A., Williams, T. W., Lin, Y., Berry, D. C., Jelicks, L. A., Lee, H., Temple, K. A., Graves, R., Pollard, J. W., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23424 · Cited by 429
Self-citationIyengar, P., Combs, T. P., Shah, S. J., Gouon–Evans, V., Pollard, J. W., Albanese, C., Flanagan, L., Tenniswood, M., Guha, C., Lisanti, M. P., et al. (2003) · Oncogene · doi:10.1038/sj.onc.1206737 · Cited by 372
Self-citationParacrine Regulation of Angiogenesis and Adipocyte Differentiation During In Vivo Adipogenesis
Fukumura, D., Ushiyama, A., Duda, D. G., Xu, L., Tam, J., Krishna, V., Chatterjee, K., Garkavtsev, I., & Jain, R. K. (2003) · Circulation Research · doi:10.1161/01.res.0000099243.20096.fa · Cited by 365
Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells
Dieudonné, M., Bussière, M., Santos, E. D., Leneveu, M.-C., Giudicelli, Y., & Pecquery, R. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.04.076 · Cited by 352
Shibata, R., Ouchi, N., Kihara, S., Sato, K., Funahashi, T., & Walsh, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402558200 · Cited by 336 · cited 3×
“Previous work has proposed a role for APN in vessel remodeling and promotion of angiogenesis in an in vivo hind limb model of ischemia (25, 37).”
BackgroundWang, Z. V., Schraw, T., Kim, J., Khan, T., Rajala, M. W., Follenzi, A., & Scherer, P. E. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00931-06 · Cited by 307
Self-citationPlasma Adiponectin Concentrations and Risk of Incident Breast Cancer
Tworoger, S. S., Eliassen, A. H., Kelesidis, T., Colditz, G. A., Willett, W. C., Mantzoros, C. S., & Hankinson, S. E. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1975 · Cited by 284
Wang, Y., Lam, J. B. B., Lam, K. S. L., Liu, J., Lam, M. C., Hoo, R. L. C., Wu, D., Cooper, G. J. S., & Xu, A. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1969 · Cited by 270
Ruzinova, M. B., Schoer, R. A., Gerald, W. L., Egan, J. E., Pandolfi, P. P., Rafii, S., Manova, K., Mittal, V., & Benezra, R. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00240-x · Cited by 244
Hebbard, L., Garlatti, M., Young, L. J. T., Cardiff, R. D., Oshima, R. G., & Ranscht, B. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-2953 · Cited by 172
Sengenès, C., Miranville, A., Maumus, M., Barros, S. D., Busse, R., & Bouloumié, A. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0180 · Cited by 124
Emoto, M., Anno, T., Satō, Y., Tanabe, K., Okuya, S., Tanizawa, Y., Matsutani, A., & Oka, Y. (2001) · Diabetes · doi:10.2337/diabetes.50.5.1166 · Cited by 92
Sikder, H. A., Huso, D. L., Zhang, H., Wang, B., Ryu, B., Hwang, S. T., Powell, J. D., & Alani, R. M. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00245-9 · Cited by 78
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Egeblad, M., Nakasone, E. S., & Werb, Z. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.05.012 · Cited by 1,294
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Metadata
- Authors
- Landskroner-Eiger, S., Qian, B., Muise, E. S., Nawrocki, A. R., Berger, J. P., Fine, E. J., Koba, W., Deng, Y., Pollard, J. W., & Scherer, P. E.
- Affiliations
- 1Cell Biology, Departments of
- 2Developmental and Molecular Biology, Center of Reproductive Biology and Womens' Health, Albert Einstein Cancer Center, and
- 4Molecular Profiling and
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Albert Einstein College of Medicine (US)
- The University of Texas Southwestern Medical Center (US)
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2009-05-15
- Volume
- 15
- Issue
- 10
- Pages
- 3265-3276
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC3237387
- OpenAlex
- W2118763988
- Cited by
- 145
- References
- 51
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 12 · 2016: 7 · 2015: 10 · 2014: 10 · 2013: 23 · 2012: 15
- FWCI
- 6.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- National Cancer Institute (R01CA112023)
- National Institute of General Medical Sciences (T32-GM04791)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- adiponectin, mammary tumor growth, tumor angiogenesis, breast cancer, adipokines, MMTV-PyMT mice, endothelial progenitor cells, tumor hypoxia, tumor microenvironment, tumor vascularization
- MeSH terms
- Animals, Antigens, Viral, Tumor, Female, Flow Cytometry, Glucose, Male, Mammary Tumor Virus, Mouse, Mammary Neoplasms, Experimental, Mice, Inbred C57BL, Neovascularization, Pathologic, Polyomavirus, Time Factors, Blotting, Western, Gene Expression Regulation, Neoplastic, Apoptosis, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Vascular Endothelial Growth Factor A, Thiazolidinediones, Tumor Burden, PPAR gamma, Positron-Emission Tomography, Mice, Adiponectin
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