Journal article
Stress Effects on FosB- and Interleukin-8 (IL8)-driven Ovarian Cancer Growth and Metastasis
The Journal of biological chemistry, Vol.285(46), pp.35462-35470
11/2010
DOI: 10.1074/jbc.M110.109579
PMID: 20826776
Abstract
A growing number of studies indicate that chronic stress can accelerate tumor growth due to sustained sympathetic nervous system activation. Our recent findings suggest that chronic stress is associated with increased IL8 levels. Here, we examined the molecular and biological significance of IL8 in stress-induced tumor growth. Norepinephrine (NE) treatment of ovarian cancer cells resulted in a 250–300% increase in IL8 protein and 240–320% increase in its mRNA levels. Epinephrine treatment resulted in similar increases. Moreover, NE treatment resulted in a 3.5–4-fold increase in IL8 promoter activity. These effects were blocked by propranolol. Promoter deletion analyses suggested that AP1 transcription factors might mediate catecholamine-stimulated up-regulation of IL8. siRNA inhibition studies identified FosB as the pivotal component responsible for IL8 regulation by NE. In vivo chronic stress resulted in increased tumor growth (by 221 and 235%; p < 0.01) in orthotopic xenograft models involving SKOV3ip1 and HeyA8 ovarian carcinoma cells. This enhanced tumor growth was completely blocked by IL8 or FosB gene silencing using 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine nanoliposomes. IL8 and FosB silencing reduced microvessel density (based on CD31 staining) by 2.5- and 3.5-fold, respectively (p < 0.001). Our findings indicate that neurobehavioral stress leads to FosB-driven increases in IL8, which is associated with increased tumor growth and metastases. These findings may have implications for ovarian cancer management.
Details
- Title: Subtitle
- Stress Effects on FosB- and Interleukin-8 (IL8)-driven Ovarian Cancer Growth and Metastasis
- Creators
- Mian M.K Shahzad - From the Departments of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030Jesusa M Arevalo - the Division of Hematology-Oncology, Department of Medicine, UCLA, Los Angeles, California 90095Guillermo N Armaiz-Pena - From the Departments of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030Chunhua Lu - From the Departments of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030Rebecca L Stone - From the Departments of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030Myrthala Moreno-Smith - From the Departments of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030Masato Nishimura - From the Departments of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030Jeong-Won Lee - From the Departments of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030Nicholas B Jennings - From the Departments of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030Justin Bottsford-Miller - From the Departments of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030Pablo Vivas-Mejia - Experimental Therapeutics, and University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030Susan K Lutgendorf - the Department of Psychology, University of Iowa, Iowa City, Iowa 52241Gabriel Lopez-Berestein - Experimental Therapeutics, and University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030Menashe Bar-Eli - Cancer Biology and University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030Steven W Cole - the Division of Hematology-Oncology, Department of Medicine, UCLA, Los Angeles, California 90095Anil K Sood - From the Departments of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.285(46), pp.35462-35470
- DOI
- 10.1074/jbc.M110.109579
- PMID
- 20826776
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 11/2010
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute; Obstetrics and Gynecology; Urology
- Record Identifier
- 9984065768702771
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