Journal article
Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma
Nature medicine, Vol.12(8), pp.939-944
08/2006
DOI: 10.1038/nm1447
PMID: 16862152
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.
Details
- Title: Subtitle
- Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma
- Creators
- Anil K Sood - Department of Gynecologic Oncology, University of Texas (U.T.) M.D. Anderson Cancer Center Department of Cancer Biology, U.T. M.D. Anderson Cancer CenterAparna A Kamat - Department of Gynecologic Oncology, University of Texas (U.T.) M.D. Anderson Cancer CenterNicholas B Jennings - Department of Gynecologic Oncology, University of Texas (U.T.) M.D. Anderson Cancer CenterRobert L Coleman - Department of Gynecologic Oncology, University of Texas (U.T.) M.D. Anderson Cancer CenterMurali Ravoori - Department of Experimental Diagnostic Imaging, U.T. M.D. Anderson Cancer CenterAngela M Sanguino - Department of Experimental Therapeutics, U.T. M.D. Anderson Cancer CenterRie Takahashi - Division of Hematology-Oncology, Department of Medicine, 11-934 Factor Building, University of California Los Angeles (UCLA) School of MedicineLingegowda S Mangala - Department of Gynecologic Oncology, University of Texas (U.T.) M.D. Anderson Cancer CenterJesusa M Arevalo - Division of Hematology-Oncology, Department of Medicine, 11-934 Factor Building, University of California Los Angeles (UCLA) School of MedicineRobert A Newman - Department of Experimental Therapeutics, U.T. M.D. Anderson Cancer CenterMary Lloyd - Department of Cancer Biology, U.T. M.D. Anderson Cancer CenterPremal H Thaker - Department of Gynecologic Oncology, University of Texas (U.T.) M.D. Anderson Cancer CenterCharles N Landen - Department of Gynecologic Oncology, University of Texas (U.T.) M.D. Anderson Cancer CenterJames A Bankson - Department of Imaging Physics, U.T. M.D. Anderson Cancer CenterYang Li - Department of Gynecologic Oncology, University of Texas (U.T.) M.D. Anderson Cancer CenterSteven W Cole - Division of Hematology-Oncology, Department of Medicine, 11-934 Factor Building, University of California Los Angeles (UCLA) School of MedicineEdward Felix - Department of Experimental Therapeutics, U.T. M.D. Anderson Cancer CenterVikas Kundra - Department of Experimental Diagnostic Imaging, U.T. M.D. Anderson Cancer Center Department of Diagnostic Radiology, U.T. M.D. Anderson Cancer CenterDavid M Gershenson - Department of Gynecologic Oncology, University of Texas (U.T.) M.D. Anderson Cancer CenterChunhua Lu - Department of Gynecologic Oncology, University of Texas (U.T.) M.D. Anderson Cancer CenterTae Jin Kim - Department of Gynecologic Oncology, University of Texas (U.T.) M.D. Anderson Cancer CenterLiz Y Han - Department of Gynecologic Oncology, University of Texas (U.T.) M.D. Anderson Cancer CenterSusan K Lutgendorf - Department of Psychology, University of Iowa, E228 Seashore HallWilliam M Merritt - Department of Gynecologic Oncology, University of Texas (U.T.) M.D. Anderson Cancer CenterGabriel Lopez-Berestein - Department of Experimental Therapeutics, U.T. M.D. Anderson Cancer CenterYvonne G Lin - Department of Gynecologic Oncology, University of Texas (U.T.) M.D. Anderson Cancer CenterGuillermo Armaiz-Pena - Department of Gynecologic Oncology, University of Texas (U.T.) M.D. Anderson Cancer Center
- Resource Type
- Journal article
- Publication Details
- Nature medicine, Vol.12(8), pp.939-944
- DOI
- 10.1038/nm1447
- PMID
- 16862152
- NLM abbreviation
- Nat Med
- ISSN
- 1078-8956
- eISSN
- 1546-170X
- Language
- English
- Date published
- 08/2006
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute; Obstetrics and Gynecology; Urology
- Record Identifier
- 9984065888102771
Metrics
33 Record Views