High dose fractionated ionizing radiation inhibits prostate cancer cell adhesion and beta(1) integrin expression.
BACKGROUND
The effect of ionizing radiation on extracellular matrix (ECM)-mediated cellular functions is an important area of research for translational science. Mechanisms of tumor cell ability to proliferate, migrate, and survive appear dependent on integrin-mediated adhesion to the ECM; however, the exact role therapeutic radiation plays in altering signaling pathways and promoting cell death within remains less well established.


METHODS
To examine these effects on prostate carcinoma cell lines, cells were irradiated at sub-lethal doses. We have studied two human prostate cancer cell lines (PC3 and DU-145) irradiated with different fractionated radiation schedules. Three groups were compared to non-irradiated controls. Group A was given a single dose of 5 Gy. Group B was given 5 Gy the first week and then 10 Gy the second week for a total of 15 Gy. Group C was given 5 Gy the first week, and then 10 Gy the second and third week for a total of 25 Gy. Cells were analyzed at their prescribed total dose. At 48 hr post irradiation, cells were detached from culture dishes and were subsequently used for adhesion assays and immunoblotting analysis.


RESULTS
Our findings revealed that two prostate carcinoma cell lines, PC3 and DU-145, had a reduced cellular adhesion to fibronectin (FN) compared to the non-irradiated control groups. Both prostate cancer cell lines showed decreased adhesion to FN and reduced beta(1) integrin protein levels at a total dose of 25 Gy, but not at the doses of 15 and 5 Gy. In a parallel analysis, at the maximum total dose of 25 Gy, both PC3 and DU-145 demonstrated a significant decrease in cell proliferation.


CONCLUSIONS
High dose radiation treatment of prostate cancer cell lines inhibits integrin expression. Our study suggests that promoting a synergistic decrease in adhesion could bring additional therapeutic benefit to patients treated with radiation therapy.
Simon
Edmund L
EL
Department of Radiation Oncology, University of Massachusetts Memorial Health Care Hospitals, Worcester, Massachusetts 01605, USA.
Goel
Hira L
HL
Teider
Natalia
N
Wang
Tao
T
Languino
Lucia R
LR
Fitzgerald
T J
TJ
D017209:Apoptosis / Q000528:radiation effects; D002448:Cell Adhesion / Q000528:radiation effects*; D002455:Cell Division / Q000528:radiation effects; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D005353:Fibronectins / Q000378:metabolism; D005456:Fluorescent Dyes; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D011829:Radiation Dosage; D012235:Rhodamines
D005353:Fibronectins; D005456:Fluorescent Dyes; D019012:Integrin beta1; D012235:Rhodamines; C022027:lissamine rhodamine B