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Glucocorticoids indirectly decrease colon cancer cell proliferation and invasion via effects on cancer-associated fibroblasts

Zuzanna Drebert (UGent) , Elly De Vlieghere (UGent) , Jolien Bridelance (UGent) , Olivier De Wever (UGent) , Karolien De Bosscher (UGent) , Marc Bracke (UGent) and Ilse Beck (UGent)
(2017) EXPERIMENTAL CELL RESEARCH. 362(2). p.332-342
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Abstract
Cancer-associated fibroblasts (CAFs) support cancer growth, invasion, and metastasis. Glucocorticoids (GCs), drugs often administered together with chemotherapy, are steroidal ligands of the glucocorticoid receptor (GR), a transcription factor which upon activation regulates expression of multiple genes involved in suppression of inflammation. We have previously shown that in dexamethasone (Dex)-treated CAFs derived from colon cancer, production and secretion of several factors related to cancer progression, such as tenascin C (TNC) and hepatocyte growth factor (HGF), were strongly suppressed. In this study we show that GCs can neutralize the cancer cell-promoting properties of CAFs. Conditioned medium from solvent-treated CAFs (CMCTRL) stimulates proliferation, motility and stretched morphotype of GR-deficient HCT8/E11 colon cancer cells. Yet, HCT8/E11 proliferation and stretched morphotype are impaired upon treatment with conditioned medium from Dex-treated CAFs (CMDEX), but HCT8/E11 cell migration is slightly increased under these conditions. Moreover, expression and potential activity of MMP-2 is also reduced in CMDEX compared with CMCTRL. These combined in vitro results concur with the results from in vivo chick chorioallantoic membrane assays, where the co-cultures of CAFs with colon cancer cells displayed impaired tumor formation and cancer cell invasion due to Dex administration. Combined, GC treatment influences cancer cell behavior indirectly through effects on CAFs.
Keywords
Glucocorticoids, Cancer-associated fibroblasts (CAFs), Colon cancer, Cancer cell proliferation, Cancer cell invasion, TUMOR MICROENVIRONMENT, COLORECTAL-CANCER, BREAST-CANCER, RECEPTOR, MYOFIBROBLASTS, MECHANISMS, RESISTANCE, GROWTH, TRANSITION, MIGRATION

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MLA
Drebert, Zuzanna et al. “Glucocorticoids Indirectly Decrease Colon Cancer Cell Proliferation and Invasion via Effects on Cancer-associated Fibroblasts.” EXPERIMENTAL CELL RESEARCH 362.2 (2017): 332–342. Print.
APA
Drebert, Z., De Vlieghere, E., Bridelance, J., De Wever, O., De Bosscher, K., Bracke, M., & Beck, I. (2017). Glucocorticoids indirectly decrease colon cancer cell proliferation and invasion via effects on cancer-associated fibroblasts. EXPERIMENTAL CELL RESEARCH, 362(2), 332–342.
Chicago author-date
Drebert, Zuzanna, Elly De Vlieghere, Jolien Bridelance, Olivier De Wever, Karolien De Bosscher, Marc Bracke, and Ilse Beck. 2017. “Glucocorticoids Indirectly Decrease Colon Cancer Cell Proliferation and Invasion via Effects on Cancer-associated Fibroblasts.” Experimental Cell Research 362 (2): 332–342.
Chicago author-date (all authors)
Drebert, Zuzanna, Elly De Vlieghere, Jolien Bridelance, Olivier De Wever, Karolien De Bosscher, Marc Bracke, and Ilse Beck. 2017. “Glucocorticoids Indirectly Decrease Colon Cancer Cell Proliferation and Invasion via Effects on Cancer-associated Fibroblasts.” Experimental Cell Research 362 (2): 332–342.
Vancouver
1.
Drebert Z, De Vlieghere E, Bridelance J, De Wever O, De Bosscher K, Bracke M, et al. Glucocorticoids indirectly decrease colon cancer cell proliferation and invasion via effects on cancer-associated fibroblasts. EXPERIMENTAL CELL RESEARCH. 2017;362(2):332–42.
IEEE
[1]
Z. Drebert et al., “Glucocorticoids indirectly decrease colon cancer cell proliferation and invasion via effects on cancer-associated fibroblasts,” EXPERIMENTAL CELL RESEARCH, vol. 362, no. 2, pp. 332–342, 2017.
@article{8545381,
  abstract     = {Cancer-associated fibroblasts (CAFs) support cancer growth, invasion, and metastasis. Glucocorticoids (GCs), drugs often administered together with chemotherapy, are steroidal ligands of the glucocorticoid receptor (GR), a transcription factor which upon activation regulates expression of multiple genes involved in suppression of inflammation. We have previously shown that in dexamethasone (Dex)-treated CAFs derived from colon cancer, production and secretion of several factors related to cancer progression, such as tenascin C (TNC) and hepatocyte growth factor (HGF), were strongly suppressed. 
In this study we show that GCs can neutralize the cancer cell-promoting properties of CAFs. Conditioned medium from solvent-treated CAFs (CMCTRL) stimulates proliferation, motility and stretched morphotype of GR-deficient HCT8/E11 colon cancer cells. Yet, HCT8/E11 proliferation and stretched morphotype are impaired upon treatment with conditioned medium from Dex-treated CAFs (CMDEX), but HCT8/E11 cell migration is slightly increased under these conditions. Moreover, expression and potential activity of MMP-2 is also reduced in CMDEX compared with CMCTRL. These combined in vitro results concur with the results from in vivo chick chorioallantoic membrane assays, where the co-cultures of CAFs with colon cancer cells displayed impaired tumor formation and cancer cell invasion due to Dex administration. Combined, GC treatment influences cancer cell behavior indirectly through effects on CAFs.},
  author       = {Drebert, Zuzanna and De Vlieghere, Elly and Bridelance, Jolien and De Wever, Olivier and De Bosscher, Karolien and Bracke, Marc and Beck, Ilse},
  issn         = {0014-4827},
  journal      = {EXPERIMENTAL CELL RESEARCH},
  keywords     = {Glucocorticoids,Cancer-associated fibroblasts (CAFs),Colon cancer,Cancer cell proliferation,Cancer cell invasion,TUMOR MICROENVIRONMENT,COLORECTAL-CANCER,BREAST-CANCER,RECEPTOR,MYOFIBROBLASTS,MECHANISMS,RESISTANCE,GROWTH,TRANSITION,MIGRATION},
  language     = {eng},
  number       = {2},
  pages        = {332--342},
  title        = {Glucocorticoids indirectly decrease colon cancer cell proliferation and invasion via effects on cancer-associated fibroblasts},
  url          = {http://dx.doi.org/10.1016/j.yexcr.2017.11.034},
  volume       = {362},
  year         = {2017},
}

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