Journal article
Biobehavioral modulation of the exosome transcriptome in ovarian carcinoma
Cancer, Vol.124(3), pp.580-586
02/01/2018
DOI: 10.1002/cncr.31078
PMCID: PMC5780197
PMID: 29112229
Abstract
BACKGROUND Social factors in the patient macroenvironment have been shown to influence molecular events in the tumor microenvironment and thereby influence cancer progression. However, biomarkers providing a window into the longitudinal effects of biobehavioral factors on tumor biology over time are lacking. Exosome analysis is a novel strategy for in vivo monitoring of dynamic changes in tumor cells. This study examined exosomal profiles from patients with low or high levels of social support for epithelial‐mesenchymal transition (EMT) polarization and gene expression related to inflammation and β‐adrenergic signaling. METHODS Exosomes were isolated from plasma sampled from a series of 40 women before primary surgical resection of advanced‐stage, high‐grade ovarian carcinoma. Samples were selected for analysis on the basis of extremes of low and high levels of social support. After exosomal isolation and RNA extraction, a microarray analysis of the transcriptome was performed. RESULTS Primary analyses identified significant upregulation of 67 mesenchymal‐characteristic gene transcripts and downregulation of 63 epithelial‐characteristic transcripts in patients with low social support; this demonstrated increased EMT polarization (P = .0002). Secondary analyses using promoter sequence bioinformatics supported a priori hypotheses linking low social support to 1) increased activity of cyclic adenosine monophosphate response element binding protein (CREB)/activating transcription factor (ATF) family transcription factors that mediate the β‐adrenergic response to catecholamines via the cyclic adenosine monophosphate/protein kinase A signaling pathway (mean fold change for CREB: 2.24 ± 0.65; P = .0019; mean fold change for ATF: 2.00 ± 0.55; P = .0049) and 2) increased activity of the proinflammatory nuclear factor κB/Rel family of transcription factors (mean fold change: 2.10 ± 0.70; P = .0109). CONCLUSIONS These findings suggest the possibility of leveraging exosomes as a noninvasive assessment of biobehavioral factors to help to direct personalized treatment approaches. Cancer 2018;124:580‐6. © 2017 American Cancer Society. This study leverages transcriptome profiling of exosomes to investigate relations between the social support level of the patient and his or her tumor biology. Primary analyses have identified significant upregulation of 67 mesenchymal‐characteristic gene transcripts and downregulation of 63 epithelial characteristic transcripts in patients with low levels of social support, and this demonstrates decreased epithelial‐mesenchymal transition polarization in this group.
Details
- Title: Subtitle
- Biobehavioral modulation of the exosome transcriptome in ovarian carcinoma
- Creators
- Susan K Lutgendorf - University of IowaPremal H Thaker - Washington University School of MedicineJesusa M Arevalo - University of CaliforniaMichael J Goodheart - University of IowaGeorge M Slavich - University of CaliforniaAnil K Sood - The University of Texas MD Anderson Cancer CenterSteve W Cole - University of California
- Resource Type
- Journal article
- Publication Details
- Cancer, Vol.124(3), pp.580-586
- DOI
- 10.1002/cncr.31078
- PMID
- 29112229
- PMCID
- PMC5780197
- NLM abbreviation
- Cancer
- ISSN
- 0008-543X
- eISSN
- 1097-0142
- Number of pages
- 7
- Grant note
- National Institutes of Health (CA193249 ; CA140933 ; CA109298 ; AG017265 ; AG043404 ; P30CA086862) National Institute on Aging
- Language
- English
- Date published
- 02/01/2018
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute; Obstetrics and Gynecology; Urology
- Record Identifier
- 9983931477202771
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