RNA-seq analysis reveals significant effects of EGFR signalling on the secretome of mesenchymal stem cells

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12 Citations (Scopus)

Abstract

Bone marrow-derived mesenchymal stem cells (MSCs) contribute to breast cancer progression by releasing soluble factors that sustain tumor progression. MSCs express functional epidermal growth factor receptor (EGFR) and breast cancer cells secrete EGFR-ligands including transforming growth factor-α (TGFα). Using RNAsequencing, we analysed the whole transcriptome of MSCs stimulated with TGFα. We identified 1,640 highly differentially regulated genes: 967 genes up-regulated with Fold Induction (FI)≥1.50 and 673 genes down-regulated with FI≤0.50. When highly regulated genes were categorized according to GO molecular function classification and KEGG pathways analysis, a large number of genes coding for potentially secreted proteins or surface receptors resulted enriched following TGFα treatment, including VEGFA, IL6, EREG, HB-EGF, LIF, NGF, NRG1, CCL19, CCL2, CCL25 and CXCL3. Secretion of corresponding proteins was confirmed for selected factors. Finally, we identified 4,377 and 4,262 alternatively spliced genes in untreated and TGFα-treated MSCs, respectively. Among these, an unannotated splice variant of VEGFA coding for a secreted VEGF protein of 172 aminoacids (VEGFA172), was found only in MSCs stimulated with TGFα. These findings suggest that EGFR activation in MSCs leads to a significant change in the expression of a wide array of genes coding for secreted proteins that can significantly enhance tumor progression.

Original languageEnglish
Pages (from-to)10518-10528
Number of pages11
JournalOncotarget
Volume5
Issue number21
Publication statusPublished - 2014

Fingerprint

Mesenchymal Stromal Cells
Epidermal Growth Factor Receptor
Transforming Growth Factors
RNA
Genes
Breast Neoplasms
Proteins
Recombinant DNA
Nerve Growth Factor
Transcriptome
Vascular Endothelial Growth Factor A
Interleukin-6
Neoplasms
Membrane Proteins
Bone Marrow
Ligands

Keywords

  • EGFR
  • Mesenchymal stem cells
  • RNA-seq
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology

Cite this

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title = "RNA-seq analysis reveals significant effects of EGFR signalling on the secretome of mesenchymal stem cells",
abstract = "Bone marrow-derived mesenchymal stem cells (MSCs) contribute to breast cancer progression by releasing soluble factors that sustain tumor progression. MSCs express functional epidermal growth factor receptor (EGFR) and breast cancer cells secrete EGFR-ligands including transforming growth factor-α (TGFα). Using RNAsequencing, we analysed the whole transcriptome of MSCs stimulated with TGFα. We identified 1,640 highly differentially regulated genes: 967 genes up-regulated with Fold Induction (FI)≥1.50 and 673 genes down-regulated with FI≤0.50. When highly regulated genes were categorized according to GO molecular function classification and KEGG pathways analysis, a large number of genes coding for potentially secreted proteins or surface receptors resulted enriched following TGFα treatment, including VEGFA, IL6, EREG, HB-EGF, LIF, NGF, NRG1, CCL19, CCL2, CCL25 and CXCL3. Secretion of corresponding proteins was confirmed for selected factors. Finally, we identified 4,377 and 4,262 alternatively spliced genes in untreated and TGFα-treated MSCs, respectively. Among these, an unannotated splice variant of VEGFA coding for a secreted VEGF protein of 172 aminoacids (VEGFA172), was found only in MSCs stimulated with TGFα. These findings suggest that EGFR activation in MSCs leads to a significant change in the expression of a wide array of genes coding for secreted proteins that can significantly enhance tumor progression.",
keywords = "EGFR, Mesenchymal stem cells, RNA-seq, Tumor microenvironment",
author = "{De Luca}, Antonella and Cristin Roma and Marianna Gallo and Francesca Fenizia and Francesca Bergantino and Daniela Frezzetti and Susan Costantini and Nicola Normanno",
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T1 - RNA-seq analysis reveals significant effects of EGFR signalling on the secretome of mesenchymal stem cells

AU - De Luca, Antonella

AU - Roma, Cristin

AU - Gallo, Marianna

AU - Fenizia, Francesca

AU - Bergantino, Francesca

AU - Frezzetti, Daniela

AU - Costantini, Susan

AU - Normanno, Nicola

PY - 2014

Y1 - 2014

N2 - Bone marrow-derived mesenchymal stem cells (MSCs) contribute to breast cancer progression by releasing soluble factors that sustain tumor progression. MSCs express functional epidermal growth factor receptor (EGFR) and breast cancer cells secrete EGFR-ligands including transforming growth factor-α (TGFα). Using RNAsequencing, we analysed the whole transcriptome of MSCs stimulated with TGFα. We identified 1,640 highly differentially regulated genes: 967 genes up-regulated with Fold Induction (FI)≥1.50 and 673 genes down-regulated with FI≤0.50. When highly regulated genes were categorized according to GO molecular function classification and KEGG pathways analysis, a large number of genes coding for potentially secreted proteins or surface receptors resulted enriched following TGFα treatment, including VEGFA, IL6, EREG, HB-EGF, LIF, NGF, NRG1, CCL19, CCL2, CCL25 and CXCL3. Secretion of corresponding proteins was confirmed for selected factors. Finally, we identified 4,377 and 4,262 alternatively spliced genes in untreated and TGFα-treated MSCs, respectively. Among these, an unannotated splice variant of VEGFA coding for a secreted VEGF protein of 172 aminoacids (VEGFA172), was found only in MSCs stimulated with TGFα. These findings suggest that EGFR activation in MSCs leads to a significant change in the expression of a wide array of genes coding for secreted proteins that can significantly enhance tumor progression.

AB - Bone marrow-derived mesenchymal stem cells (MSCs) contribute to breast cancer progression by releasing soluble factors that sustain tumor progression. MSCs express functional epidermal growth factor receptor (EGFR) and breast cancer cells secrete EGFR-ligands including transforming growth factor-α (TGFα). Using RNAsequencing, we analysed the whole transcriptome of MSCs stimulated with TGFα. We identified 1,640 highly differentially regulated genes: 967 genes up-regulated with Fold Induction (FI)≥1.50 and 673 genes down-regulated with FI≤0.50. When highly regulated genes were categorized according to GO molecular function classification and KEGG pathways analysis, a large number of genes coding for potentially secreted proteins or surface receptors resulted enriched following TGFα treatment, including VEGFA, IL6, EREG, HB-EGF, LIF, NGF, NRG1, CCL19, CCL2, CCL25 and CXCL3. Secretion of corresponding proteins was confirmed for selected factors. Finally, we identified 4,377 and 4,262 alternatively spliced genes in untreated and TGFα-treated MSCs, respectively. Among these, an unannotated splice variant of VEGFA coding for a secreted VEGF protein of 172 aminoacids (VEGFA172), was found only in MSCs stimulated with TGFα. These findings suggest that EGFR activation in MSCs leads to a significant change in the expression of a wide array of genes coding for secreted proteins that can significantly enhance tumor progression.

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