ArticleMolecular cancer2010
The impact of stress on tumor growth: peripheral CRF mediates tumor-promoting effects of stress.
Article in Molecular cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 27 citations in OpenAlex.
- Article
- A unifying theory of brain signaling and its possible role in acquired chronic disease.Frontiers in neuroscience · 2026Article
- Expression of Corticotropin-Releasing Hormone and Its Receptors May Be Associated With Survival Rate in Pancreatic Cancer.Gastro hep advances · 2023Article
- Effect of chronic stress on tumorigenesis and development.Cellular and molecular life sciences : CMLS · 2022Review
- Psychologic Stress Drives Progression of Malignant Tumors via DRD2/HIF1α Signaling.Cancer research · 2021Article
- Chronic stress promotes EMT-mediated metastasis through activation of STAT3 signaling pathway by miR-337-3p in breast cancer.Cell death & disease · 2020Article
- Chronic Stress Promotes Cancer Development.Frontiers in oncology · 2020Review
- Analgesics promote welfare and sustain tumour growth in orthotopic 4T1 and B16 mouse cancer models.Laboratory animals · 2018Article
- The influence of marital status on the stage at diagnosis, treatment, and survival of adult patients with gastric cancer: a population-based study.Oncotarget · 2017Article
- Synthesis, F-18 radiolabeling, and microPET evaluation of 3-(2,4-dichlorophenyl)-N-alkyl-N-fluoroalkyl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amines as ligands of the corticotropin-releasing factor type-1 (CRF1) receptor.Bioorganic & medicinal chemistry · 2015Article
- Immunolocalization of corticotropin-releasing hormone (CRH) and its receptors (CRHR1 and CRHR2) in human endometrial carcinoma: CRHR1 as a potent prognostic factor.International journal of gynecological cancer : official journal of the International Gynecological Cancer Society · 2014Article
- Corticotropin-releasing factor reduces tumor volume, halts further growth, and enhances the effect of chemotherapy in 4T1 mammary carcinoma in mice.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
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Abstract
introductionStress has been shown to be a tumor promoting factor. Both clinical and laboratory studies have shown that chronic stress is associated with tumor growth in several types of cancer. Corticotropin Releasing Factor (CRF) is the major hypothalamic mediator of stress, but is also expressed in peripheral tissues. Earlier studies have shown that peripheral CRF affects breast cancer cell proliferation and motility. The aim of the present study was to assess the significance of peripheral CRF on tumor growth as a mediator of the response to stress in vivo.
methodsFor this purpose we used the 4T1 breast cancer cell line in cell culture and in vivo. Cells were treated with CRF in culture and gene specific arrays were performed to identify genes directly affected by CRF and involved in breast cancer cell growth. To assess the impact of peripheral CRF as a stress mediator in tumor growth, Balb/c mice were orthotopically injected with 4T1 cells in the mammary fat pad to induce breast tumors. Mice were subjected to repetitive immobilization stress as a model of chronic stress. To inhibit the action of CRF, the CRF antagonist antalarmin was injected intraperitoneally. Breast tissue samples were histologically analyzed and assessed for neoangiogenesis.
resultsArray analysis revealed among other genes that CRF induced the expression of SMAD2 and β-catenin, genes involved in breast cancer cell proliferation and cytoskeletal changes associated with metastasis. Cell transfection and luciferase assays confirmed the role of CRF in WNT- β-catenin signaling. CRF induced 4T1 cell proliferation and augmented the TGF-β action on proliferation confirming its impact on TGFβ/SMAD2 signaling. In addition, CRF promoted actin reorganization and cell migration, suggesting a direct tumor-promoting action. Chronic stress augmented tumor growth in 4T1 breast tumor bearing mice and peripheral administration of the CRF antagonist antalarmin suppressed this effect. Moreover, antalarmin suppressed neoangiogenesis in 4T1 tumors in vivo.
conclusionThis is the first report demonstrating that peripheral CRF, at least in part, mediates the tumor-promoting effects of stress and implicates CRF in SMAD2 and β-catenin expression.
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