Journal article
Biobehavioral Influences on Matrix Metalloproteinase Expression in Ovarian Carcinoma
Clinical cancer research, Vol.14(21), pp.6839-6846
2008
DOI: 10.1158/1078-0432.CCR-08-0230
PMCID: PMC2716059
PMID: 18980978
Abstract
Purpose: Stromal cells in the tumor microenvironment, such as macrophages, play an active role in tumor growth and angiogenesis. However, little is known about relationships of biobehavioral factors with angiogenic cytokines and matrix metalloproteinases (MMP) produced by stromal cells. This study examined distress, MMPs, and angiogenic cytokines in ovarian cancer patients and in vitro.
Experimental design: Patients suspected of ovarian cancer completed preoperative questionnaires. At surgery, 56 were confirmed to have epithelial ovarian cancer. Tumor samples were analyzed for macrophage (CD68(+)) and tumor cell levels of MMP-2, MMP-9, and vascular endothelial growth factor. In vitro stimulation of isolated macrophage cells by the stress hormones norepinephrine and cortisol was done to assess effects on MMP-9.
Results: Depressed patients showed significant elevations of MMP-9 in CD68(+) cells, adjusting for stage (P<0.0001). Patients with higher levels of current stress (P=0.01), life stress over the last 6 months (P=0.004), and general negative affect (P=0.007) also showed significantly greater MMP-9 in CD68(+) cells. In contrast, higher social support was associated with lower levels of MMP-9 (P=0.023) and vascular endothelial growth factor (P=0.036) in tumor cells. In vitro analyses showed that macrophage MMP-9 production could be directly enhanced (up to a 2-fold increase) by the stress hormones norepinephrine and cortisol.
Conclusions: Ovarian cancer patients with elevated depressive symptoms, chronic stress, and low social support showed elevations in MMP-9 in tumor-associated macrophages. Direct in vitro enhancement of stromal MMP-9 production by stress hormones was also shown. These findings may have implications for patient outcomes in ovarian cancer.
Details
- Title: Subtitle
- Biobehavioral Influences on Matrix Metalloproteinase Expression in Ovarian Carcinoma
- Creators
- Susan K LUTGENDORF - Department of Psychology, University of Iowa, United StatesDonald M LAMKIN - Department of Psychology, University of Iowa, United StatesAnil K SOOD - Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United StatesNicholas B JENNINGS - Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United StatesJesusa M. G AREVALO - Division of Hematology-Oncology, David Geffen School of Medicine, University of California at Los Angeles School of Medicine, United StatesFrank PENEDO - Department of Psychology, University of Miami, Miami, Florida, United StatesKoen DEGEEST - Department of Obstetrics and Gynecology, University of Iowa, United StatesRobert R LANGLEY - Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United StatesJoseph A LUCCILLL - Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, United StatesSteve W COLE - The Norman Cousins Center, Jonsson Comprehensive Cancer Center, University of California at Los Angeles AIDS Institute, and University of California at Los Angeles Molecular Biology Institute, Los Angeles, California, United StatesDavid M LUBAROFF - Department of Microbiology, University of Iowa, United States
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.14(21), pp.6839-6846
- DOI
- 10.1158/1078-0432.CCR-08-0230
- PMID
- 18980978
- PMCID
- PMC2716059
- NLM abbreviation
- Clin Cancer Res
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Publisher
- American Association for Cancer Research; Philadelphia, PA
- Language
- English
- Date published
- 2008
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute; Obstetrics and Gynecology; Urology
- Record Identifier
- 9984065886702771
Metrics
23 Record Views