scholarly journals Surgical Wound Fluids from Patients with Breast Cancer Reveal Similarities in the Biological Response Induced by Intraoperative Radiation Therapy and the Radiation-Induced Bystander Effect—Transcriptomic Approach

2020 ◽  
Vol 21 (3) ◽  
pp. 1159
Author(s):  
Kulcenty ◽  
Piotrowski ◽  
Rucinski ◽  
Wroblewska ◽  
Jopek ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Bystander Effect ◽  
Gene Set Enrichment Analysis ◽  
Cell Phenotype ◽  
Biological Processes ◽  
Surgical Wound ◽  
Wound Fluid ◽  
Radiation Induced ◽  
Radiation Induced Bystander Effect

In patients with breast cancer who undergo breast-conserving surgery (BCS), more than 90% of local recurrences occur in the same quadrant as the primary cancer. Surgical wound fluids (SWF) are believed to play a role in this process by inducing an inflammatory process in the scar tissue area. Despite strong clinical data demonstrating the benefits of intraoperative radiotherapy (IORT), the biological basis underlying this process remains poorly understood. Ionizing radiation (IR) directly affects cells by damaging DNA, thereby altering the cell phenotype. IR directly affects cancer cells and also influences unirradiated cells located nearby, a phenomenon known as the radiation-induced bystander effect (RIBE), significantly modifying the tumor microenvironment. We hypothesized that SWF obtained from patients after BCS and IORT would induce a radiobiological response (due to RIBE) in unirradiated cells, thereby modifying their phenotype. To confirm this hypothesis, breast cancer cells were incubated with SWF collected from patients after BCS: (1) without IORT (wound fluid (WF) group), (2) with IORT (radiotherapy wound fluid (RT-WF) group), and (3) WF with conditioned medium from irradiated cells (WF+RIBE group) and then subjected to microarray analysis. We performed gene set enrichment analysis to determine the biological processes present in these cells. This analysis showed that the RT-WF and WF+RIBE groups shared common biological processes, including the enhancement of processes involved in cell-cycle regulation, DNA repair, and oxidative phosphorylation. The WF group was characterized by overrepresentation of pathways involved in the INF-α and INF-γ response, inflammatory response, and the IL6 JAK/STAT3 signaling pathway. These findings show that MDA-MB-468 cells stimulated with surgical wound fluids obtained from patients who underwent BCS plus IORT and from cells stimulated with SWF plus RIBE share common biological processes. This confirms the role of the radiation-induced bystander effect in altering the biological properties of wound fluids.

scholarly journals The Antiproliferative Effects of Progestins in T47D Breast Cancer Cells Are Tempered by Progestin Induction of the ETS Transcription Factor Elf5

2010 ◽  
Vol 24 (7) ◽  
pp. 1380-1392 ◽  
Author(s):  
H. N. Hilton ◽  
M. Kalyuga ◽  
M. J. Cowley ◽  
M. C. Alles ◽  
H. J. Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Gene Set Enrichment Analysis ◽  
Cell Phenotype ◽  
Cell Cycle Gene ◽  
Antiproliferative Effects ◽  
Ets Transcription Factor

Abstract Prolactin and progesterone act together to regulate mammary alveolar development, and both hormones have been implicated in breast cancer initiation and progression. Here we show that Elf5, a prolactin-induced ETS transcription factor that specifies the mammary secretory cell lineage, is also induced by progestins in breast cancer cells via a direct mechanism. To define the transcriptional response to progestin elicited via Elf5, we made an inducible Elf5 short hairpin-RNA knock-down model in T47D breast cancer cells and used it to prevent the progestin-induction of Elf5. Functional analysis of Affymetrix gene expression data using Gene Ontologies and Gene Set Enrichment Analysis showed enhancement of the progestin effects on cell cycle gene expression. Cell proliferation assays showed a more efficacious progestin-induced growth arrest when Elf5 was kept at baseline levels. These results showed that progestin induction of Elf5 expression tempered the antiproliferative effects of progestins in T47D cells, providing a further mechanistic link between prolactin and progestin in the regulation of mammary cell phenotype.

scholarly journals A radiosensitizer, gallotannin-rich extract from Bouea macrophylla seeds, inhibits radiation-induced epithelial-mesenchymal transition in breast cancer cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiraporn Kantapan ◽  
Siwaphon Paksee ◽  
Aphidet Duangya ◽  
Padchanee Sangthong ◽  
Sittiruk Roytrakul ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Cell Death ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Breast Cancer Cell Lines ◽  
Mesenchymal Transition ◽  
Mammosphere Formation ◽  
Radiation Induced

Abstract Background Radioresistance can pose a significant obstacle to the effective treatment of breast cancers. Epithelial–mesenchymal transition (EMT) is a critical step in the acquisition of stem cell traits and radioresistance. Here, we investigated whether Maprang seed extract (MPSE), a gallotannin-rich extract of seed from Bouea macrophylla Griffith, could inhibit the radiation-induced EMT process and enhance the radiosensitivity of breast cancer cells. Methods Breast cancer cells were pre-treated with MPSE before irradiation (IR), the radiosensitizing activity of MPSE was assessed using the colony formation assay. Radiation-induced EMT and stemness phenotype were identified using breast cancer stem cells (CSCs) marker (CD24−/low/CD44+) and mammosphere formation assay. Cell motility was determined via the wound healing assay and transwell migration. Radiation-induced cell death was assessed via the apoptosis assay and SA-β-galactosidase staining for cellular senescence. CSCs- and EMT-related genes were confirmed by real-time PCR (qPCR) and Western blotting. Results Pre-treated with MPSE before irradiation could reduce the clonogenic activity and enhance radiosensitivity of breast cancer cell lines with sensitization enhancement ratios (SERs) of 2.33 and 1.35 for MCF7 and MDA-MB231cells, respectively. Pretreatment of breast cancer cells followed by IR resulted in an increased level of DNA damage maker (γ-H2A histone family member) and enhanced radiation-induced cell death. Irradiation induced EMT process, which displayed a significant EMT phenotype with a down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker vimentin in comparison with untreated breast cancer cells. Notably, we observed that pretreatment with MPSE attenuated the radiation-induced EMT process and decrease some stemness-like properties characterized by mammosphere formation and the CSC marker. Furthermore, pretreatment with MPSE attenuated the radiation-induced activation of the pro-survival pathway by decrease the expression of phosphorylation of ERK and AKT and sensitized breast cancer cells to radiation. Conclusion MPSE enhanced the radiosensitivity of breast cancer cells by enhancing IR-induced DNA damage and cell death, and attenuating the IR-induced EMT process and stemness phenotype via targeting survival pathways PI3K/AKT and MAPK in irradiated breast cancer cells. Our findings describe a novel strategy for increasing the efficacy of radiotherapy for breast cancer patients using a safer and low-cost natural product, MPSE.

scholarly journals Mechanism of radiation-induced bystander effect: Role of the cyclooxygenase-2 signaling pathway

2005 ◽  
Vol 102 (41) ◽  
pp. 14641-14646 ◽  
Author(s):  
H. Zhou ◽  
V. N. Ivanov ◽  
J. Gillespie ◽  
C. R. Geard ◽  
S. A. Amundson ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Bystander Effect ◽  
Cyclooxygenase 2 ◽  
Radiation Induced ◽  
Radiation Induced Bystander Effect

scholarly journals Radiation-induced bystander effect in non-irradiated glioblastoma spheroid cells

2015 ◽  
Vol 56 (5) ◽  
pp. 777-783 ◽  
Author(s):  
Fahime Faqihi ◽  
Ali Neshastehriz ◽  
Shokouhozaman Soleymanifard ◽  
Robabeh Shabani ◽  
Nazila Eivazzadeh
Keyword(s):  
Bystander Effect ◽  
Radiation Induced ◽  
Radiation Induced Bystander Effect

scholarly journals Regulation of Ionizing Radiation-Induced Adhesion of Breast Cancer Cells to Fibronectin by Alpha5beta1 Integrin

2014 ◽  
Vol 181 (6) ◽  
pp. 650-658 ◽  
Author(s):  
Shin Hee Lee ◽  
Huiwen Cheng ◽  
Ye Yuan ◽  
Shiyong Wu
Keyword(s):  
Breast Cancer ◽  
Ionizing Radiation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Radiation Induced
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