Biobehavioral influences on matrix metalloproteinase expression in ovarian carcinoma
Open accessAbstract
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.
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Social isolation, stress, and depression are linked to biological processes that drive tumor progression and lower survival.
“Additionally, factors such as social isolation, stress, and depression are associated with key biological processes promoting tumor progression and poorer survival.”
From Living Well: Protocol for a web-based program to improve quality of life in rural and urban ovarian cancer survivors (2024) · cites this paper as [12]
The Results and Discussion (page not provided) link depression and stress to elevated macrophage MMP-9, and lower social support to tumor-cell MMP-9 and VEGF—factors the paper describes as supporting angiogenesis and invasion. The Conclusion says these mechanisms could have implications for survival, but the study does not establish an association with poorer survival. (LLM, conf=0.88)
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Self-citation
- Authors
- Lutgendorf, S. K., Lamkin, D. M., Jennings, N. B., Arevalo, J. M. G., Penedo, F., DeGeest, K., Langley, R. R., Lucci, J. A., Cole, S. W., Lubaroff, D. M., & Sood, A. K.
- Affiliations
- University of Iowa (US)
- 1Psychology, Departments of
- 6Gynecologic Oncology and
- University of California, Los Angeles (US)
- University of Miami (US)
- 2Obstetrics and Gynecology, and
- The University of Texas MD Anderson Cancer Center (US)
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2008-11-01
- Volume
- 14
- Issue
- 21
- Pages
- 6839-6846
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC2716059
- OpenAlex
- W2163747854
- Cited by
- 158
- References
- 49
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 6 · 2023: 9 · 2022: 11 · 2021: 9 · 2020: 5 · 2019: 6 · 2018: 9 · 2017: 7 · 2016: 16 · 2015: 14 · 2014: 10 · 2013: 10 · 2012: 12
- FWCI
- 5.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (CA 109298, R21CA088293, R01CA110793, CA 110793, CA-104825, R01CA109298, R01CA104825, P50CA083639)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Keywords
- ovarian carcinoma, MMP-9, MMP-2, tumor-associated macrophages, tumor microenvironment, depressive symptoms, chronic stress, social support, vascular endothelial growth factor, norepinephrine, cortisol, angiogenic cytokines, CD68
- MeSH terms
- Adult, Aged, Aged, 80 and over, Behavior, Depression, Female, Humans, Hydrocortisone, Macrophages, Middle Aged, Norepinephrine, Ovarian Neoplasms, Social Support, Stress, Psychological, Mood Disorders, Matrix Metalloproteinases
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