Page 267 - 2014 Printable Abstract Book
P. 267
in 30 fractions over a period of 6 weeks. By exposing the 3D multicell cocultures to 2 Gy daily doses of
radiation for 5 and 10 days, the aggressiveness of the spheroid models containing the lung cancer stem
cells may be assessed via clonogenic assay. Pimonidazole, a hypoxia marker, is being used to evaluate the
distribution of hypoxic cells co-culture incorporating the CSC. We expect that the in vitro 3D NSCLC co-
culture system that incorporates characteristics of the tumor microenvironment and tumor cell
heterogeneity will provide a robust and enhanced model for understanding the multifactorial nature of
radioresistance in tumors.
(PS4-53) Radiation response and radiation-induced bystander signaling in human glioblastoma cells:
effects on self-renewal and differentiation of neural stem cells. Vladimir N. Ivanov, PhD and Tom K. Hei,
PhD, Center for Radiological Research, New York, NY
Ionizing radiation alone or in combination with chemotherapy is the main treatment modality for
brain tumors, including glioblastomas. Adult neurons and astrocytes, as terminally differentiated cells,
demonstrate substantial radioresistance. In contrast, human neural stem cells (NSC) are highly sensitive
to ionizing radiation. Cranial irradiation may directly induce death of NSC causing substantial cognitive
deficiency. Glioblastomas are extremely active in secretion of numerous proteins, including cytokines,
growth factors and death ligands that dramatically affect brain function. The main goal of our study was
to determine effects of glioblastoma secreted factors, as components of tumor micro-environment, on
self-renewal and differentiation of neural stem cells before and after irradiation. Using media transfer
experiments from conditioned and irradiated U87MG glioblastoma cells, we observed pronounced time-
dependent effects of the glioblastoma secretome on apoptosis of the naïve NSC. Surprisingly, conditioned
U87MG media already induced high levels of apoptosis of NSC that was additionally induced after
irradiated media transfer. Dramatic upregulation of production of IL8, TGF-beta and IL6 in cancer cells
after irradiation could partially neutralize action of death ligand (TRAIL) on NSC. Neural and glial pathways
of NSC differentiation were initiated by the corresponding differentiation media. Eight hours of
pretreatment of the naive NSC by irradiated glioblastoma media dramatically suppressed the subsequent
neuronal differentiation, while did not stop glial differentiation. Both IL8 and TGF-beta1 increased
precursor cell survival, but caused retardation of neuronal differentiation. On the other hand, IL6 appears
to be involved in surviving and differentiation of young astrocytes. We established U87MG spheroid
population that was strongly enriched by SOX2-positive, CD133-positive cells, which considered being
cancer stem cells (CSC). Radiation substantially upregulated apoptotic death levels among CSC. Media
transfer experiments from non-treated and irradiated CSC to the naïve NSC further confirmed induction
of apoptosis in NSC. Intercellular communication between cancer cells and NSC could be involved in
amplification of cancer pathology in the brain.
(PS4-54) Characterization of radiation quality effects on human mammary lineage commitment.
Raheleh Hatami, PhD and Mary Helen Barcellos-Hoff, PhD, NYUMC, New York, NY
Women treated with radiation for childhood cancers are more likely to develop aggressive and
less differentiated, triple negative breast cancers. Based on the “cell of origin” hypothesis, these tumors
arise from pluripotent stem/progenitor cells. We showed that radiation induces Notch, β-catenin, and
TGFβ to increase mammary stem cell frequency in the mouse mammary gland, as well as cells with
265 | P a g e
radiation for 5 and 10 days, the aggressiveness of the spheroid models containing the lung cancer stem
cells may be assessed via clonogenic assay. Pimonidazole, a hypoxia marker, is being used to evaluate the
distribution of hypoxic cells co-culture incorporating the CSC. We expect that the in vitro 3D NSCLC co-
culture system that incorporates characteristics of the tumor microenvironment and tumor cell
heterogeneity will provide a robust and enhanced model for understanding the multifactorial nature of
radioresistance in tumors.
(PS4-53) Radiation response and radiation-induced bystander signaling in human glioblastoma cells:
effects on self-renewal and differentiation of neural stem cells. Vladimir N. Ivanov, PhD and Tom K. Hei,
PhD, Center for Radiological Research, New York, NY
Ionizing radiation alone or in combination with chemotherapy is the main treatment modality for
brain tumors, including glioblastomas. Adult neurons and astrocytes, as terminally differentiated cells,
demonstrate substantial radioresistance. In contrast, human neural stem cells (NSC) are highly sensitive
to ionizing radiation. Cranial irradiation may directly induce death of NSC causing substantial cognitive
deficiency. Glioblastomas are extremely active in secretion of numerous proteins, including cytokines,
growth factors and death ligands that dramatically affect brain function. The main goal of our study was
to determine effects of glioblastoma secreted factors, as components of tumor micro-environment, on
self-renewal and differentiation of neural stem cells before and after irradiation. Using media transfer
experiments from conditioned and irradiated U87MG glioblastoma cells, we observed pronounced time-
dependent effects of the glioblastoma secretome on apoptosis of the naïve NSC. Surprisingly, conditioned
U87MG media already induced high levels of apoptosis of NSC that was additionally induced after
irradiated media transfer. Dramatic upregulation of production of IL8, TGF-beta and IL6 in cancer cells
after irradiation could partially neutralize action of death ligand (TRAIL) on NSC. Neural and glial pathways
of NSC differentiation were initiated by the corresponding differentiation media. Eight hours of
pretreatment of the naive NSC by irradiated glioblastoma media dramatically suppressed the subsequent
neuronal differentiation, while did not stop glial differentiation. Both IL8 and TGF-beta1 increased
precursor cell survival, but caused retardation of neuronal differentiation. On the other hand, IL6 appears
to be involved in surviving and differentiation of young astrocytes. We established U87MG spheroid
population that was strongly enriched by SOX2-positive, CD133-positive cells, which considered being
cancer stem cells (CSC). Radiation substantially upregulated apoptotic death levels among CSC. Media
transfer experiments from non-treated and irradiated CSC to the naïve NSC further confirmed induction
of apoptosis in NSC. Intercellular communication between cancer cells and NSC could be involved in
amplification of cancer pathology in the brain.
(PS4-54) Characterization of radiation quality effects on human mammary lineage commitment.
Raheleh Hatami, PhD and Mary Helen Barcellos-Hoff, PhD, NYUMC, New York, NY
Women treated with radiation for childhood cancers are more likely to develop aggressive and
less differentiated, triple negative breast cancers. Based on the “cell of origin” hypothesis, these tumors
arise from pluripotent stem/progenitor cells. We showed that radiation induces Notch, β-catenin, and
TGFβ to increase mammary stem cell frequency in the mouse mammary gland, as well as cells with
265 | P a g e
