Page 259 - 2014 Printable Abstract Book
P. 259
after irradiation at 2 Gy, the intestinal stem cells exhibited increased proliferative activity,
misdifferentiation, and γH2AvD and 8-oxo-dG levels. In addition, the guts irradiated with 2 Gy showed
increased JNK and AKT activities. Furthermore, we showed that 2 Gy of IR induce centrosome
amplification in ISCs of adult midguts. Our data give molecular insights into the effects of ionizing radiation
on functional modifications of stem cells. The adult Drosophila midgut intestinal stem cells offer a
paradigm for the exploration of the biological effects of ionizing radiation.
(PS4-40) IL-6 promotes stemness of cancer stem cells and may contribute to radiation resistance of non-
small cell lung cancer. Yuhchyau Chen, MD, PhD; Ying Tsai, MS; Laura R. Strojny, BS; Jong-Wei Hsu, PhD;
Shan-Zhou Duan, MD; Peter C. Keng, PhD; and Soo Ok Lee, PhD, University of Rochester, Rochester, NY
Lung cancer is the leading cause of cancer-related deaths among both men and women. Long-
term survival of lung cancer patients remains low despite aggressive therapies including surgery,
radiation, and chemotherapy. Radiotherapy is the standard primary treatment for patients diagnosed with
localized unresectable non-small cell lung cancer (NSCLC). However, local tumor control by standard
fractionated radiotherapy (RT) remains very poor despite high dose radiation to 60-74 Gy primarily due
to tumor resistance to radiation. The role of cancer stem cells (CSCs) in mediating radiation resistance
(radioresistance) has been suggested, but not well understood for NSCLC. In this study, we investigated
the role of IL-6 in CSCs mediated radioresistance of NSCLC. We found that irradiation (6 Gy) increased
CD133+ CSC population in 3 NSCLC cell lines, and especially, such increase was more in IL-6 secreting cells
than non-IL-6 secreting cells. We also found that the CD133+ CSC population in NSCLC cells could be
increased by IL-6 treatment. Interestingly, when we analyzed the CSC population increase in IL-6 knocked
down vs. scramble control (sc) A549 and H157 cells upon irradiation (6 Gy), we found the extent of CD133+
CSC increase was lower in IL-6 knocked down cells than that of the corresponding control cells, suggesting
that IL-6 contributed to the increase of CSC upon irradiation. This could be due to the role of IL-6 in
promoting CSC growth as we found significantly less growth of the CD133+ CSCs isolated from IL-6
knocked down A549 cells than control cells after irradiation. Consistently, we also found lower
proliferative index (Ki-67) and higher apoptosis of CD133+ CSCs isolated from the IL-6 knocked down A549
cells after irradiation than control cells. Overall, our data suggest that IL-6 may contribute to NSCLC-CSC
mediated-radioresistance via promoting self-renewal and stemness of the survived CSCs, thereby
increasing CSC population after irradiation. In light of higher radioresistance, higher tumorigenic and
metastatic ability of CSCs, our finding of the role of IL-6 in promoting the growth of CSC population may
have clinical relevance, in that combining RT with agents that block IL-6 signaling (or its downstream
signaling) can potentially reduce NSCLC-CSC-mediated radioresistance and improve cancer control.
(PS4-41) First visualization of the cancer stem cell niche for solid tumors and the effects of radiation
dose on its architecture. Christopher S. Lange, D.Phil.; Talal Syed; Mike Zhang; Christian Sabalvaro; Hana
Lim, MD; Ghadir Salame, MD; Albert J. Palileo, MD; Michelle Chan; and Catherine Li, SUNY Downstate Med
Ctr, Brooklyn, NY
The recent paradigm shift towards targeted cancer stem cell (CSC) therapy has necessitated the
development of a model of the CSC microenvironment, or niche. Study of the niche may elucidate the
mechanisms by which CSCs function in their maintenance and growth of the tumor. Niche characterization
257 | P a g e
misdifferentiation, and γH2AvD and 8-oxo-dG levels. In addition, the guts irradiated with 2 Gy showed
increased JNK and AKT activities. Furthermore, we showed that 2 Gy of IR induce centrosome
amplification in ISCs of adult midguts. Our data give molecular insights into the effects of ionizing radiation
on functional modifications of stem cells. The adult Drosophila midgut intestinal stem cells offer a
paradigm for the exploration of the biological effects of ionizing radiation.
(PS4-40) IL-6 promotes stemness of cancer stem cells and may contribute to radiation resistance of non-
small cell lung cancer. Yuhchyau Chen, MD, PhD; Ying Tsai, MS; Laura R. Strojny, BS; Jong-Wei Hsu, PhD;
Shan-Zhou Duan, MD; Peter C. Keng, PhD; and Soo Ok Lee, PhD, University of Rochester, Rochester, NY
Lung cancer is the leading cause of cancer-related deaths among both men and women. Long-
term survival of lung cancer patients remains low despite aggressive therapies including surgery,
radiation, and chemotherapy. Radiotherapy is the standard primary treatment for patients diagnosed with
localized unresectable non-small cell lung cancer (NSCLC). However, local tumor control by standard
fractionated radiotherapy (RT) remains very poor despite high dose radiation to 60-74 Gy primarily due
to tumor resistance to radiation. The role of cancer stem cells (CSCs) in mediating radiation resistance
(radioresistance) has been suggested, but not well understood for NSCLC. In this study, we investigated
the role of IL-6 in CSCs mediated radioresistance of NSCLC. We found that irradiation (6 Gy) increased
CD133+ CSC population in 3 NSCLC cell lines, and especially, such increase was more in IL-6 secreting cells
than non-IL-6 secreting cells. We also found that the CD133+ CSC population in NSCLC cells could be
increased by IL-6 treatment. Interestingly, when we analyzed the CSC population increase in IL-6 knocked
down vs. scramble control (sc) A549 and H157 cells upon irradiation (6 Gy), we found the extent of CD133+
CSC increase was lower in IL-6 knocked down cells than that of the corresponding control cells, suggesting
that IL-6 contributed to the increase of CSC upon irradiation. This could be due to the role of IL-6 in
promoting CSC growth as we found significantly less growth of the CD133+ CSCs isolated from IL-6
knocked down A549 cells than control cells after irradiation. Consistently, we also found lower
proliferative index (Ki-67) and higher apoptosis of CD133+ CSCs isolated from the IL-6 knocked down A549
cells after irradiation than control cells. Overall, our data suggest that IL-6 may contribute to NSCLC-CSC
mediated-radioresistance via promoting self-renewal and stemness of the survived CSCs, thereby
increasing CSC population after irradiation. In light of higher radioresistance, higher tumorigenic and
metastatic ability of CSCs, our finding of the role of IL-6 in promoting the growth of CSC population may
have clinical relevance, in that combining RT with agents that block IL-6 signaling (or its downstream
signaling) can potentially reduce NSCLC-CSC-mediated radioresistance and improve cancer control.
(PS4-41) First visualization of the cancer stem cell niche for solid tumors and the effects of radiation
dose on its architecture. Christopher S. Lange, D.Phil.; Talal Syed; Mike Zhang; Christian Sabalvaro; Hana
Lim, MD; Ghadir Salame, MD; Albert J. Palileo, MD; Michelle Chan; and Catherine Li, SUNY Downstate Med
Ctr, Brooklyn, NY
The recent paradigm shift towards targeted cancer stem cell (CSC) therapy has necessitated the
development of a model of the CSC microenvironment, or niche. Study of the niche may elucidate the
mechanisms by which CSCs function in their maintenance and growth of the tumor. Niche characterization
257 | P a g e
