Page 261 - 2014 Printable Abstract Book
P. 261
vasculogenesis when tip cells have motile protrusive structures and are creating pioneer guidance tunnels
through the matrix. High LET charged particles do not affect the early stages of vasculogenesis but they
do affect the later stages when the endothelial cells migrate to form tubes.
1
(PS4-43) Radiation exposure increases mammary stem cell self-renewal in Balb/c mice. Daisuke Iizuka ;
1
2
1
Megumi Sasatani ; Mary Helen Barcellos-Hoff ; and Kenji Kamiya, Department of Experimental Oncology,
1
Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan and
Departments of Radiation Oncology and Cell Biology, New York University School of Medicine, New York,
NY 2
Tissue stem cells including those of the mammary gland are thought to have an important role in
susceptibility to tumorigenesis. The epidemiological study of A-bomb survivors has suggested that the
excess absolute risk for breast cancer incidence is higher than that for any other sites. Experimental
studies suggest that investigating the biological effect of ionizing radiation on mammary stem cells is
important for understanding cancer risk. Previous studies have demonstrated that relatively low-dose
radiation exposure (100-1,000 mGy) increased mammary stem cell self-renewal in juvenile BALB/c mice
(Nguyen DH et al., Cancer Cell 2011, Tang H et al., Stem Cells 2014). Interestingly, neither increasing dose
nor using HZE particle radiation elicit greater effect, suggesting that the mechanism of self-renewal is not
due to cell kill or other direct effects. To clarify the potential biological effect of chronic radiation
exposure, we investigated threshold radiation dose and dose-rate dependence of this phenomenon and
the strain-dependence of this phenomenon. Here we determined threshold dose/dose-rate and
investigated the strain difference of this phenomenon using mammary epithelial cells isolated
enzymatically and then analyzed with FACS and in vitro limiting dilution assay for mammosphere
formation to assay the mammary stem cell self-renewal in both BALB/c and C57BL/6 mice. Four-week old
BALB/c and C57BL/6 mice were gamma-irradiated at high (185 mGy/min) or middle (1 mGy/min) dose-
rate. Preliminary data replicate the prior reports of a 2-fold increased mammary stem cell assays in cells
from juvenile BALB/c mice irradiated with 100 or 1,000 mGy. However mammary stem cells did not
increase when C57BL/6 mice were irradiated at high dose rate with 100 or 1,000 mGy or when BALB/c
mice were exposed to less than 100 mGy. Reducing the dose rate at which BALB/c mice were exposed to
100 mGy also failed to elicit increased mammary stem cell markers or mammospheres. These data suggest
a threshold between 50 and 100 mGy and dose rate dependence for this tissue response. In support of
the relationship between stem cell dysregulation and carcinogenesis, mammary tumor resistant C57BL/6
mice do not exhibit increased mammary stem cells. Additional ongoing experiments extending these
studies will be reported.
1
(PS4-44) Radiation-induced glioblastoma stem cells migration. Sabrina Boyrie ; Sylvie Monferran ;
2
2
2
1
2
Caroline Delmas ; Christine Toulas ; and Elizabeth Cohen-Jonathan-Moyal, UCLA, Los Angeles, CA and
institut Claudius regaud, toulouse, France
2
Background: Despite combined modality treatment associating surgery and radiochemotherapy,
glioblastoma recurs in the radiation fields or at distance in the brain parenchyma. Within the tumor,
glioblastoma stem cells (GSC), which are more invasive than their differentiated progeny cells, have been
proposed to be responsible for the tumour recurrence. We hypothesized that GSC migration was
259 | P a g e
through the matrix. High LET charged particles do not affect the early stages of vasculogenesis but they
do affect the later stages when the endothelial cells migrate to form tubes.
1
(PS4-43) Radiation exposure increases mammary stem cell self-renewal in Balb/c mice. Daisuke Iizuka ;
1
2
1
Megumi Sasatani ; Mary Helen Barcellos-Hoff ; and Kenji Kamiya, Department of Experimental Oncology,
1
Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan and
Departments of Radiation Oncology and Cell Biology, New York University School of Medicine, New York,
NY 2
Tissue stem cells including those of the mammary gland are thought to have an important role in
susceptibility to tumorigenesis. The epidemiological study of A-bomb survivors has suggested that the
excess absolute risk for breast cancer incidence is higher than that for any other sites. Experimental
studies suggest that investigating the biological effect of ionizing radiation on mammary stem cells is
important for understanding cancer risk. Previous studies have demonstrated that relatively low-dose
radiation exposure (100-1,000 mGy) increased mammary stem cell self-renewal in juvenile BALB/c mice
(Nguyen DH et al., Cancer Cell 2011, Tang H et al., Stem Cells 2014). Interestingly, neither increasing dose
nor using HZE particle radiation elicit greater effect, suggesting that the mechanism of self-renewal is not
due to cell kill or other direct effects. To clarify the potential biological effect of chronic radiation
exposure, we investigated threshold radiation dose and dose-rate dependence of this phenomenon and
the strain-dependence of this phenomenon. Here we determined threshold dose/dose-rate and
investigated the strain difference of this phenomenon using mammary epithelial cells isolated
enzymatically and then analyzed with FACS and in vitro limiting dilution assay for mammosphere
formation to assay the mammary stem cell self-renewal in both BALB/c and C57BL/6 mice. Four-week old
BALB/c and C57BL/6 mice were gamma-irradiated at high (185 mGy/min) or middle (1 mGy/min) dose-
rate. Preliminary data replicate the prior reports of a 2-fold increased mammary stem cell assays in cells
from juvenile BALB/c mice irradiated with 100 or 1,000 mGy. However mammary stem cells did not
increase when C57BL/6 mice were irradiated at high dose rate with 100 or 1,000 mGy or when BALB/c
mice were exposed to less than 100 mGy. Reducing the dose rate at which BALB/c mice were exposed to
100 mGy also failed to elicit increased mammary stem cell markers or mammospheres. These data suggest
a threshold between 50 and 100 mGy and dose rate dependence for this tissue response. In support of
the relationship between stem cell dysregulation and carcinogenesis, mammary tumor resistant C57BL/6
mice do not exhibit increased mammary stem cells. Additional ongoing experiments extending these
studies will be reported.
1
(PS4-44) Radiation-induced glioblastoma stem cells migration. Sabrina Boyrie ; Sylvie Monferran ;
2
2
2
1
2
Caroline Delmas ; Christine Toulas ; and Elizabeth Cohen-Jonathan-Moyal, UCLA, Los Angeles, CA and
institut Claudius regaud, toulouse, France
2
Background: Despite combined modality treatment associating surgery and radiochemotherapy,
glioblastoma recurs in the radiation fields or at distance in the brain parenchyma. Within the tumor,
glioblastoma stem cells (GSC), which are more invasive than their differentiated progeny cells, have been
proposed to be responsible for the tumour recurrence. We hypothesized that GSC migration was
259 | P a g e
