In vitro evidence for the potential of EGFR inhibitors to decrease the TGF-β1-induced dispersal of circulating tumour cell clusters mediated by EGFR overexpression.
Jorian D HapemanRakshit GalwaCaroline S CarneiroAurora M NedelcuPublished in: Scientific reports (2024)
Most cancer-related deaths are due to the spread of tumour cells throughout the body-a process known as metastasis. While in the vasculature, these cells are referred to as circulating tumour cells (CTCs) and can be found as either single cells or clusters of cells (often including platelets), with the latter having the highest metastatic potential. However, the biology of CTC clusters is poorly understood, and there are no therapies that specifically target them. We previously developed an in vitro model system for CTC clusters and proposed a new extravasation model that involves cluster dissociation, adherence, and single-cell invasion in response to TGF-β1 released by platelets. Here, we investigated TGF-β1-induced gene expression changes in this model, focusing on genes for which targeted drugs are available. In addition to the upregulation of the TGF-β1 signalling pathway, we found that (i) genes in the EGF/EGFR pathway, including those coding for EGFR and several EGFR ligands, were also induced, and (ii) Erlotinib and Osimertinib, two therapeutic EGFR/tyrosine kinase inhibitors, decreased the TGF-β1-induced adherence and invasion of the CTC cluster-like line despite the line expressing wild-type EGFR. Overall, we suggest that EGFR inhibitors have the potential to decrease the dispersal of CTC clusters that respond to TGF-β1 and overexpress EGFR (irrespective of its status) and thus could improve patient survival.
Keyphrases
- small cell lung cancer
- epidermal growth factor receptor
- induced apoptosis
- tyrosine kinase
- cell cycle arrest
- transforming growth factor
- gene expression
- high glucose
- circulating tumor cells
- endoplasmic reticulum stress
- diabetic rats
- stem cells
- advanced non small cell lung cancer
- squamous cell carcinoma
- signaling pathway
- adipose tissue
- metabolic syndrome
- cell death
- drug delivery
- epithelial mesenchymal transition
- poor prognosis
- skeletal muscle
- insulin resistance
- endothelial cells
- dna methylation
- wild type
- risk assessment
- climate change
- cell free
- long non coding rna