TY - JOUR
T1 - Radiation modulates expression and related activities of c-Met protein in oral tongue squamous cell carcinoma cell lines
AU - Al-Jamaei, Aisha A. H.
AU - de Visscher, Jan G. A. M.
AU - Forouzanfar, Tymour
AU - Brakenhoff, Ruud H.
AU - Leemans, C. Rene
AU - Stikvoort, Arwen
AU - Zandieh-Doulabi, Behrouz
AU - Helder, Marco N.
N1 - Funding Information: Authors are grateful to Prof. Venkata Subramanyam Ramadugula of K M Shah Dental College and Hospital, Sumandeep Vidyapeeth, Vadodara, Gujarat, India for his help in editing the manuscript. We also would like to thank Mr. Henk van der Berg for his assistance in viability assay experiments. Our thanks go finally to Sander A. Snel and Jennifer Sckeick for their help in flow cytometry analysis. Publisher Copyright: © 2022, The Author(s).
PY - 2023/7
Y1 - 2023/7
N2 - Objectives: c-Met, a receptor tyrosine kinase, is involved in the growth, invasion and metastasis of a variety of cancers. In a set of cell lines from several solid tumors, a five-fold increase in c-Met expression after irradiation has been reported. This study aimed to assess if c-Met is likewise abundantly expressed in oral tongue squamous cell carcinoma (OTSCC) upon exposure to irradiation, followed by a Met-induced biological response. Materials and methods: Six OTSCC cell lines were exposed to gamma radiation doses of 2, 4, and 6 Gray. The changes in c-Met protein levels were assessed by western blot and flow cytometry. c-Met gene expression, cell migration, proliferation and cell cycle assays were performed as phenotypic readouts. Results: Irradiation resulted in upregulation of c.Met in all cell lines with different time kinetics. On average the cells displayed minimal c-Met expression on their surface ranging from 5 to 30% of total protein. Abrupt downregulation of c-Met surface expression occurred one hour after radiation but recovered 48 h post-radiation. Intracellularly, the highest level of expression was found on day 5 after radiation exposure. Irradiation induced aggressive invasive potential of the cells as determined in cell migration assays, particularly in cell lines with the highest c-Met expression. Conclusions: These results provide novel insights into both intracellular and extracellular dynamics of c-Met expression profiles upon irradiation of OTSCC cells in vitro. It might also suggest that radiation enhances cell migration, indicative of invasiveness, through c-Met up-regulation, at least for certain types of OTSCC cells.
AB - Objectives: c-Met, a receptor tyrosine kinase, is involved in the growth, invasion and metastasis of a variety of cancers. In a set of cell lines from several solid tumors, a five-fold increase in c-Met expression after irradiation has been reported. This study aimed to assess if c-Met is likewise abundantly expressed in oral tongue squamous cell carcinoma (OTSCC) upon exposure to irradiation, followed by a Met-induced biological response. Materials and methods: Six OTSCC cell lines were exposed to gamma radiation doses of 2, 4, and 6 Gray. The changes in c-Met protein levels were assessed by western blot and flow cytometry. c-Met gene expression, cell migration, proliferation and cell cycle assays were performed as phenotypic readouts. Results: Irradiation resulted in upregulation of c.Met in all cell lines with different time kinetics. On average the cells displayed minimal c-Met expression on their surface ranging from 5 to 30% of total protein. Abrupt downregulation of c-Met surface expression occurred one hour after radiation but recovered 48 h post-radiation. Intracellularly, the highest level of expression was found on day 5 after radiation exposure. Irradiation induced aggressive invasive potential of the cells as determined in cell migration assays, particularly in cell lines with the highest c-Met expression. Conclusions: These results provide novel insights into both intracellular and extracellular dynamics of c-Met expression profiles upon irradiation of OTSCC cells in vitro. It might also suggest that radiation enhances cell migration, indicative of invasiveness, through c-Met up-regulation, at least for certain types of OTSCC cells.
KW - Oral tongue squamous cell carcinoma
KW - Radiation effect
KW - Radiotherapy
KW - Tongue neoplasms
KW - Tumor invasion
KW - c-Met expression
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U2 - https://doi.org/10.1007/s00432-022-04307-4
DO - https://doi.org/10.1007/s00432-022-04307-4
M3 - Article
C2 - 36053327
SN - 0171-5216
VL - 149
SP - 4173
EP - 4184
JO - Journal of Cancer Research and Clinical Oncology
JF - Journal of Cancer Research and Clinical Oncology
IS - 8
ER -