Epithelial-mesenchymal crosstalk induces radioresistance in HNSCC cells

Steinbichler, Teresa Bernadette; Abdelmoez, Alshaimaa; Maria, Metzler Veronika; Dejaco, Daniel; Riechelmann, Herbert; Dudás, József; Skvortsova, Ira

doi:10.18632/oncotarget.23248

Cited by 26 publications

(34 citation statements)

References 50 publications

(68 reference statements)

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“…3). These findings might be clinical relevant as we were able to demonstrate before that EMC-CM led to chemotherapy and radiotherapy resistance in HNSCC cells, indicating that this hybrid epithelial-mesenchymal phenotype might be involved in therapy resistance, which is also described as a key feature of CSC [4,5,40].…”

Section: Discussionmentioning

confidence: 53%

“…For the production of EMC-conditioned medium (EMC-CM), 4 × 10 4 SCC-25 or Detroit 562 cells/ml and 1 × 10 4 HGF cells/ ml were plated in 250 ml cell culture flasks and cultured for 72 h in 15 ml foetal bovine serum-containing medium (1:1 mix of DMEM/F12 (PAA) and DMEM-low glucose (PAA) supplemented with 10% foetal bovine serum (FBS) (PAA), 2 mM l-glutamine, 100 units/ml penicillin, and 100 μg/ml streptomycin) [4,5]. Then the cells were washed twice with D u l b e c c o 's P h o s p h a t e -B u ff e r e d S a l i n e ( D P B S ) (Biowhittaker®, Oud-Heverlee, Belgium) and the serumcontaining medium was replaced by 15 ml albumincontaining medium (7,5 ml DMEM/F12 (PAA) and 7,5 ml DMEM-low glucose (PAA) supplemented with bovine serum albumin (BSA, PAA) (0.4 g albumin/100 ml medium) replacing the protein content of 10% FBS, 2 mM l-glutamine, 100 units/ml penicillin, and 100 μg/ml streptomycin).…”

Section: Production Of Conditioned Mediummentioning

confidence: 99%

“…Then the cells were washed twice with D u l b e c c o 's P h o s p h a t e -B u ff e r e d S a l i n e ( D P B S ) (Biowhittaker®, Oud-Heverlee, Belgium) and the serumcontaining medium was replaced by 15 ml albumincontaining medium (7,5 ml DMEM/F12 (PAA) and 7,5 ml DMEM-low glucose (PAA) supplemented with bovine serum albumin (BSA, PAA) (0.4 g albumin/100 ml medium) replacing the protein content of 10% FBS, 2 mM l-glutamine, 100 units/ml penicillin, and 100 μg/ml streptomycin). Albumin-containing medium was left 48 h on the mixculture allowing interacting epithelial cells and fibroblasts to secrete EMC-related factors into the medium [4,5]. Afterwards, EMC-CM was collected and cells were counted.…”

Section: Production Of Conditioned Mediummentioning

confidence: 99%

“…EMC related effects include increased cancer cell mobility [2], invasiveness [2,3], acquisition of a mesenchymal phenotype (EMT) [4], generation of cells with stem-like properties and radiochemotherapy resistance [4,5]. These effects might be associated with epithelial to mesenchymal transition (EMT), but also occur without EMT meaning that EMT is just one of the effects caused by EMC [5]. In EMT, epithelial cells acquire mesenchymal characteristics under the influence of the surrounding microenvironment.…”

Section: Introductionmentioning

confidence: 99%

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Pleiotropic Effects of Epithelial Mesenchymal Crosstalk on Head and Neck Cancer: EMT and beyond

Steinbichler

Savic

Dejaco

et al. 2019

Cancer Microenvironment

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Epithelial mesenchymal crosstalk (EMC) describes the interaction of the tumor stroma and associated fibroblasts with epithelial cancer cells. In this study we analysed the effects of EMC on head and neck cancer cells. In tumor cell lines EMC was induced using media conditioned from a mix-culture of cancer cells and fibroblasts. Cell proliferation and chemotherapy response were assessed using direct cell counting. Flow cytometry, immunohistochemistry of markers of epithelial-mesenchymal transition (EMT) and subsequent TissueFaxs™ acquisition and quantification and western blot analysis were performed. Holotomographic microscopy imaging was used to visualize the effects of EMC on Cisplatin response of SCC-25 cells. EMC induced a hybrid epithelial-mesenchymal phenotype in SCC-25 cells with co-expression of vimentin and cytokeratin. This hybrid phenotype was associated with chemotherapy resistance and increased proliferation of the cells. The EMC conditioned medium led to an activation of the IL-6/STAT3 pathway with subsequent phosphorylation of STAT3. EMC induced a hybrid epithelialmesenchymal phenotype in HNSCC cells accompanied by increased therapy resistance and cell proliferation. The IL-6/ STAT3 pathway might be one of the major pathways involved in these EMC-related effects.

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Section: Discussionmentioning

confidence: 53%

Section: Production Of Conditioned Mediummentioning

confidence: 99%

Section: Production Of Conditioned Mediummentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pleiotropic Effects of Epithelial Mesenchymal Crosstalk on Head and Neck Cancer: EMT and beyond

Steinbichler

Savic

Dejaco

et al. 2019

Cancer Microenvironment

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“…Evidence linking EMT to the direct inhibition of senescence (Ansieau et al, 2008;Liu et al, 2008), promotion of radioresistance (de Jong et al, 2015;Steinbichler et al, 2018;Theys et al, 2011), and cancer stemness (Shibue and Weinberg, 2017), imply that EMT may also play an important role in the evasion of senescence, radio-tolerance, and increased clonogenic capacity that we observed in our p53-defective cells. Interestingly, the effect of CENP-A overexpression on EMT also suggests that high CENP-A levels could promote stemness, depending on p53 status.…”

Section: Cenp-a Overexpression Drives Distinct Cell Fates Depending Omentioning

confidence: 55%

CENP-A overexpression drives distinct cell fates depending on p53 status

Jeffery

Podsypanina

Gatto

et al. 2020

Preprint

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Tumour evolution is driven by both genetic and epigenetic changes. CENP-A, the centromeric histone H3 variant, is an epigenetic mark that directly perturbs genetic stability and chromatin when overexpressed. Although CENP-A overexpression is a common feature of many cancers, how this impacts cell fate and response to therapy remains unclear. Here, we established a tunable system of inducible and reversible CENP-A overexpression combined with a switch in p53 status in human cell lines. Through clonogenic survival assays and single-cell RNA-sequencing over time, we uncover the tumour suppressor p53 as a key determinant of how CENP-A impacts cell state, cell identity and therapeutic response. If p53 is functional, CENP-A overexpression promotes senescence and radiosensitivity. But, when we inactivate p53, CENP-A overexpression instead promotes epithelial-mesenchymal transition, an essential precursor for tumour cell invasion and metastasis. Thus, CENP-A overexpression drives distinct cell fates depending on p53 status, with important implications for tumour evolution.

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