Taxotere-induced elevated expression of IL8 in carcinoma-associated fibroblasts of breast invasive ductal cancer

Li, Yingliang; Rong, Guohua; Kang, Hua

doi:10.3892/ol.2017.5612

Cited by 19 publications

(16 citation statements)

References 18 publications

(20 reference statements)

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“…IL-8 is a cytokine that induces the chemotaxis of lymphocytes and neutrophils, and may promote tumor angiogenesis; the antisense nucleotide of IL-8 suppresses macrophage-induced angiogenesis, which suggests a function of IL-8 in mediating angiogenesis in inflammation and tumor progression of various types of cancer (11,30,31). A large number of clinical studies and experimental research have demonstrated that IL-8 serves critical roles in the development of breast cancer (32). Research has shown that EMT in cancer depends on comprehensive stimulation by soluble growth factors, cytokines and extracellular matrix components in the tumor microenvironment; TGF-β, FGF, EGF, IL-8 and IL-6 promotes the occurrence of EMT in various kinds of tumors.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-520c-3p negatively regulates EMT by targeting IL-8 to suppress the invasion and migration of breast cancer

et al. 2017

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Interleukin-8 (IL-8), which is secreted by cancer cells undergoing epithelial-mesenchymal transition (EMT), can promote EMT in adjacent epithelial-like cells. MicroRNAs (miRNAs/miRs) can affect the expression of target genes via binding to their 3'-untranslated regions (3'-UTRs), which may subsequently affect the biological behaviors of cancer cells. In our previous study, miR-520c-3p was predicted to directly target the 3'-UTR of IL-8. Therefore, the present study was carried out to investigate whether miR-520c-3p can interact with the IL-8 gene and regulate the EMT of breast cancer cells. Web-based prediction algorithms were used to identify miRNAs that potentially target the IL-8 transcript. Luciferase reporter assays were used to confirm the targeting of IL-8 by miR-520c-3p. Reverse transcription-quantitative PCR and western blot analyses were used to examine the levels of IL-8 and EMT-related genes in breast cancer cells. The functional impact of miR-520c-3p on EMT phenotype was evaluated using Transwell and wound-healing assays, and rescue experiments were conducted by overexpressing IL-8 to determine its effect on cell properties. miR-520c-3p was predicted by all three databases, which strongly suggested its interaction with the 3'-UTR of IL-8. The relative Renilla luciferase activity of luciferase reporter construct containing the wild-type 3'-UTR of IL-8 was markedly decreased by miR-520c-3p transfection when compared with scrambled miRNA control transfection (P<0.001). In addition, compared with the scrambled miRNA control transfection, the overexpression of miR-520c-3p significantly reduced the expression of IL-8, and resulted in increased E-cadherin and decreased vimentin and fibronectin levels in MCF-7 and T47D cells (all P<0.001). Introduction of miR-520c-3p inhibited the invasion and migration of MCF-7 and T47D cells (all P<0.001). By contrast, the rescue of IL-8 expression led to the recovery of EMT-related protein expression patterns and cell motility and invasion capabilities. In conclusion, aberrant miR-520c-3p expression may lead to reduced IL-8 expression and promote the mesenchymal phenotype in breast cancer cells, thereby increasing invasive growth.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-520c-3p negatively regulates EMT by targeting IL-8 to suppress the invasion and migration of breast cancer

et al. 2017

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“…This action was plausibly associated with overexpression of several genes involved in tumor progression, such as MCP-1, MMP-1, IL-8, RARRES-1, FGF-1, and CXCR7 in docetaxel-treated fibroblasts [45]. The pattern of cancer-promoting genes differentially expressed in CAFs before and following treatment with docetaxel is, however, much wider [46].…”

Section: Biology Of Normal Cells Upon Treatment With Platinum Derivatmentioning

confidence: 99%

Comprehensive review on how platinum- and taxane-based chemotherapy of ovarian cancer affects biology of normal cells

Mikuła-Pietrasik

Witucka

Pakuła

et al. 2018

Cell. Mol. Life Sci.

126

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One of the most neglected aspects of chemotherapy are changes, and possible consequences of these changes, that occur in normal somatic cells. In this review, we summarize effects of selected drugs used to treat ovarian cancer (platin derivatives—cisplatin and carboplatin; and taxanes—paclitaxel and docetaxel) on cellular metabolism, acquisition of reactive stroma features, cellular senescence, inflammatory reactions, apoptosis, autophagy, mitophagy, oxidative stress, DNA damage, and angiogenesis in various types of normal cells, including fibroblasts, epithelial cells, endothelial cells, and neurons. The activity of these drugs against the normal cells is presented from a broader perspective of their desirable anti-tumoral effects.

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“…MGMT-methylation is predictive of positive response to temozolomide chemotherapy, and the poor prognosis of patients with high EGR3 expression in this group does raise the question whether EGR3 is implicated in resistance to temozolomide chemotherapy. EGR3 gene expression has previously been shown to increase in breast-cancer-associated fibroblasts after treatment with taxotere 43 , and furthermore it has been shown that tissue samples from patients with recurrent breast cancer had elevated levels of EGR3 compared to the matched primary tumours 44 . In gastric and colon cancer cell lines, it has been shown that EGR3 has binding sites in several genes related to 5-fluorouracil resistance 45 .…”

Section: Discussionmentioning

confidence: 99%

Expression and prognostic value of the transcription factors EGR1 and EGR3 in gliomas

Knudsen

Eilertsen

Kielland

et al. 2020

Sci Rep

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Most glioblastoma patients have a dismal prognosis, although some survive several years. However, only few biomarkers are available to predict the disease course. EGR1 and EGR3 have been linked to glioblastoma stemness and tumour progression, and this study aimed to investigate their spatial expression and prognostic value in gliomas. Overall 207 gliomas including 190 glioblastomas were EGR1/EGR3 immunostained and quantified. A cohort of 21 glioblastomas with high P53 expression and available tissue from core and periphery was stained with double-immunofluorescence (P53-EGR1 and P53-EGR3) and quantified.EGR1 expression increased with WHO-grade, and declined by 18.9% in the tumour periphery vs. core (P = 0.01), while EGR3 expression increased by 13.8% in the periphery vs. core (P = 0.04). In patients with high EGR1 expression, 83% had methylated MGMT-promoters, while all patients with low EGR1 expression had un-methylated MGMT-promoters. High EGR3 expression in MGMT-methylated patients was associated with poor survival (HR = 1.98; 95%CI 1.22-3.22; P = 0.006), while EGR1 high/EGR3 high, was associated with poor survival vs. EGR1 high/EGR3 low (HR = 2.11; 95%CI 1.25-3.56; P = 0.005). EGR1 did not show prognostic value, but could be involved in MGMTmethylation. Importantly, EGR3 may be implicated in cell migration, while its expression levels seem to be prognostic in MGMT-methylated patients. Gliomas are the most common primary brain tumours, with the WHO grade IV glioblastoma multiforme (GBM) being the most malignant. In GBMs the current standard treatment with radical surgical resection, radiation and temozolomide therapy results in a median survival of approximately 15 months 1-3 , although some patients survive several years after diagnosis. Only few prognostic biomarkers are of use in daily practise, like the methylation status of O-6-Methylguanine-DNA Methyltransferase (MGMT) 4 and mutational status of the Isocitrate dehydrogenase 1/2 genes 5. Identification of additional novel biomarkers is therefore crucial in order to better stratify the patients. GBMs are characterized as highly vascularized, heterogeneous tumours with a profoundly infiltrative nature, leading to accelerated and aggressive disease progression. Nearly all GBMs recur after initial treatment efforts due to migrating tumour cells, which infiltrate the adjacent healthy brain parenchyma and escape surgical excision as well as radiation and temozolomide therapy. We have previously shown that these migrating tumour cells have a stem-cell like phenotype and are highly tumourigenic in vivo 6. Early growth response protein 1 (EGR1) and Early growth response protein 3 (EGR3) are C2H2-type zinc-finger proteins, which belong to the EGR-protein family of transcription factors. EGR1 has been proposed to regulate the expression of genes involved in cell proliferation, growth and cell differentiation 7,8. In addition, EGR3 has been implicated in immune regulation 9-11 and cell migration 12,13. Recently, EGR1 has been linked to the proliferation and self-rene...

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Taxotere-induced elevated expression of IL8 in carcinoma-associated fibroblasts of breast invasive ductal cancer

Abstract: Abstract. Breast cancer is the most common malignant tumor in women worldwide, and accounts for an estimated 29% of new cases and 15% of cancer-associated mortalities each year.

Cited by 19 publications

References 18 publications

MicroRNA-520c-3p negatively regulates EMT by targeting IL-8 to suppress the invasion and migration of breast cancer

MicroRNA-520c-3p negatively regulates EMT by targeting IL-8 to suppress the invasion and migration of breast cancer

Comprehensive review on how platinum- and taxane-based chemotherapy of ovarian cancer affects biology of normal cells

Expression and prognostic value of the transcription factors EGR1 and EGR3 in gliomas

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