Induction of epithelial-mesenchymal transition in thyroid follicular cells is associated with cell adhesion alterations and low-dose hyper-radiosensitivity

Abstract

BACKGROUND: Epithelial-mesenchymal transition (EMT) is associated with altered cellular adhesion. We previously demonstrated that cellular adhesion influences Low-dose Hyper-Radiosensitivity (HRS) in a variety of tumor cells. However, the relationship of low-dose HRS with the phenotypic plasticity incurred by EMT during the neoplastic transformation remains to be elucidated. OBJECTIVE: To investigate whether acquisition of EMT phenotype during progressive neoplastic transformation may affect low-dose radiation sensitivity. METHODS: Primary thyroid cells obtained from a human cystic thyroid nodule were first subjected to nutritional stress. This yielded immortalized INM-Thy1 cell strain, which was further treated with either multiple γ-radiation fractions (1.5 Gy each) or repetitive cycles of 3-methylcholanthrene and phorbol-12-myristate-13-acetate, yielding two progressive transformants, viz., INM-Thy1R and INM-Thy1C. Morphological alterations, chromosomal double-minutes, cell adhesion proteins, anchorage dependency, tumorigenicity in nude mice and cellular radiosensitivity were studied in these strains. RESULTS: Both transformants (INM-Thy1R, INM-Thy1C) displayed progressive tumorigenic features, viz., soft agar colony growth and solid tumor growth in nude mice, coupled with features of epithelial-mesenchymal transition and activated Wnt pathway. Incidentally, the chemical-induced transformant (INM-Thy1C) displayed a prominent HRS (αs/αr = 29.35) which remained unaffected at high cell density. However, the parental (INM-Thy1) cell line as well as radiation-induced transformant (INM-Thy1R) failed to show this hypersensitivity. CONCLUSION: The study shows that induction of EMT in thyroid follicular cells may accompany increased susceptibility to low-dose ionizing radiation, which was attenuated by adaptive resistance acquired during radiation-induced transformation.

A multi-gene predictive model for the radiation sensitivity of nasopharyngeal carcinoma based on machine learning

“…Furthermore, SMARCA2 is implicated in processes such as cell adhesion and cytokine response, which are tightly coupled to the interactions of tumor cells within the microenvironment. Cell adhesion influences the low-dose hyper-radiosensitivity of a broad spectrum of tumor cells, potentially further modulating their sensitivity to radiotherapy[39].…”

Targeting Cellular Plasticity: Esculetin-Driven Reversion of Stemness and EMT Phenotype in Transforming Cells with Sequential p53/p73 Knockdowns

“…Moreover, cellular plasticity is integrally associated with the emergence of intra-tumoral heterogeneity and therapy response. Such phenotypic switching has extensively been studied 1,2 during early invasive events in solid tumours widely known as Epithelial-Mesenchymal Transition (EMT). Recent evidence has indicated that a small subset of undifferentiated cells within the heterogenous population exhibit distinct features of stem cells (CSCs) as well as elevated EMT programming which function in complement to evade the cells from the primary site.…”