Lack of Radiation Dose or Quality Dependence of Epithelial-to-Mesenchymal Transition (EMT) Mediated by Transforming Growth Factor {beta}

Journal Article · Fri Apr 01 00:00:00 EDT 2011 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2010.11.058· OSTI ID:21499734

Andarawewa, Kumari L; Costes, Sylvain V ^[1]; Fernandez-Garcia, Ignacio ^[2]; Chou, William S ^[1]; Ravani, Shraddha A; Park, Howard ^[1]

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1. Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States)
2. Department of Radiation Oncology, NYU Langone School of Medicine, New York, NY (United States)

Purpose: Epithelial-to-mesenchymal transition (EMT) is a phenotype that alters cell morphology, disrupts morphogenesis, and increases motility. Our prior studies have shown that the progeny of human mammary epithelial cells (HMECs) irradiated with 2 Gy undergoes transforming growth factor {beta} (TGF-{beta})-mediated EMT. In this study we determined whether radiation dose or quality affected TGF-{beta}-mediated EMT. Methods and Materials: HMECs were cultured on tissue culture plastic or in Matrigel (BD Biosciences, San Jose, CA) and exposed to low or high linear energy transfer (LET) and TGF-{beta} (400 pg/mL). Image analysis was used to measure membrane-associated E-cadherin, a marker of functional epithelia, or fibronectin, a product of mesenchymal cells, as a function of radiation dose and quality. Results: E-cadherin was reduced in TGF-{beta}-treated cells irradiated with low-LET radiation doses between 0.03 and 2 Gy compared with untreated, unirradiated cells or TGF-{beta} treatment alone. The radiation quality dependence of TGF-{beta}-mediated EMT was determined by use of 1 GeV/amu (gigaelectron volt / atomic mass unit) {sup 56}Fe ion particles at the National Aeronautics and Space Administration's Space Radiation Laboratory. On the basis of the relative biological effectiveness of 2 for {sup 56}Fe ion particles' clonogenic survival, TGF-{beta}-treated HMECs were irradiated with equitoxic 1-Gy {sup 56}Fe ion or 2-Gy {sup 137}Cs radiation in monolayer. Furthermore, TGF-{beta}-treated HMECs irradiated with either high- or low-LET radiation exhibited similar loss of E-cadherin and gain of fibronectin and resulted in similar large, poorly organized colonies when embedded in Matrigel. Moreover, the progeny of HMECs exposed to different fluences of {sup 56}Fe ion underwent TGF-{beta}-mediated EMT even when only one-third of the cells were directly traversed by the particle. Conclusions: Thus TGF-{beta}-mediated EMT, like other non-targeted radiation effects, is neither radiation dose nor quality dependent at the doses examined.

• OSTI ID: 21499734
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 79, Issue 5; Other Information: DOI: 10.1016/j.ijrobp.2010.11.058; PII: S0360-3016(10)03682-5; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
62 RADIOLOGY AND NUCLEAR MEDICINE
CONNECTIVE TISSUE
EPITHELIUM
GROWTH FACTORS
IMAGE PROCESSING
LET
RADIATION DOSES
RADIATION QUALITY
RBE
ANIMAL TISSUES
BODY
DOSES
ENERGY TRANSFER
MITOGENS
ORGANIC COMPOUNDS
PROCESSING
PROTEINS