@article{25aea4914c4a4fe8897724a031161ffd,
title = "Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma",
abstract = "Stress can alter immunological, neurochemical and endocrinological functions, but its role in cancer progression is not well understood. Here, we show that chronic behavioral stress results in higher levels of tissue catecholamines, greater tumor burden and more invasive growth of ovarian carcinoma cells in an orthotopic mouse model. These effects are mediated primarily through activation of the tumor cell cyclic AMP (cAMP)-protein kinase A (PKA) signaling pathway by the β2 adrenergic receptor (encoded by ADRB2). Tumors in stressed animals showed markedly increased vascularization and enhanced expression of VEGF, MMP2 and MMP9, and we found that angiogenic processes mediated the effects of stress on tumor growth in vivo. These data identify β-adrenergic activation of the cAMP-PKA signaling pathway as a major mechanism by which behavioral stress can enhance tumor angiogenesis in vivo and thereby promote malignant cell growth. These data also suggest that blocking ADRB-mediated angiogenesis could have therapeutic implications for the management of ovarian cancer.",
author = "Thaker, {Premal H.} and Han, {Liz Y.} and Kamat, {Aparna A.} and Arevalo, {Jesusa M.} and Rie Takahashi and Chunhua Lu and Jennings, {Nicholas B.} and Guillermo Armaiz-Pena and Bankson, {James A.} and Murali Ravoori and Merritt, {William M.} and Lin, {Yvonne G.} and Mangala, {Lingegowda S.} and Kim, {Tae Jin} and Coleman, {Robert L.} and Landen, {Charles N.} and Yang Li and Edward Felix and Sanguino, {Angela M.} and Newman, {Robert A.} and Mary Lloyd and Gershenson, {David M.} and Vikas Kundra and Gabriel Lopez-Berestein and Lutgendorf, {Susan K.} and Cole, {Steven W.} and Sood, {Anil K.}",
note = "Funding Information: The authors thank I.J. Fidler, J. Price, C. Bucana, G. Gallick and A. Johnson for their helpful input and discussions regarding this work. We thank D. Reynolds for assistance with immunohistochemistry. We also thank J. Johnson and E. Schrock for assistance with manuscript preparation. This work was supported by US National Institutes of Health (NIH) grants (CA-11079301 and CA-10929801), the Donna Marie Cimitile-Fotheringham Award for Ovarian Cancer Research, the U.T. M.D. Anderson Ovarian Cancer SPORE (2P50 CA083639-06A1), and a Program Project Development Grant from the Ovarian Cancer Research Fund, Inc. to A.K.S., NIH grant CA-104825 to S.K.L., and NIH grant A152737 to S.W.C.",
year = "2006",
month = aug,
doi = "10.1038/nm1447",
language = "English (US)",
volume = "12",
pages = "939--944",
journal = "Nature medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "8",
}