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J Cancer Metastasis Treat 2016;2 Suppl 1

also expressed In MDA-MB-231 cells. In general, brain parenchyma) and tumor core GBM cells and
genes were more expressed in the negative population directly compared their biological differences. Our
than in the positive, highlighting the positive CSCs result showed that the invasive cells have stronger
expression of MMP-2 and MMP-9, which are related neurosphere forming efficiency in vitro in a serial
to the formation of secondary tumors. Conclusion: dilution assay and increased tumorigenic capacity
Radiation enhances the population of CSCs in different after in vivo transplantation (particularly at 100 cells/
ways according to the dose and cell line. Post-radiation, mouse) compared to the tumor core cells. A screening
a larger number and higher proportion of genes were of putative cancer stem cell markers (CD133, CD15,
expressed in the MDA-MB-231 cell line, which is more CD24/CD44, CD57 and CD117) showed that invasive
radioresistant in comparison to MCF-7. The increased GBM cells are enriched (> 2 folds) with CD57+ cells
MMP-2 and MMP-9 expression after radiation would compared to the tumor core cells, and these infiltrating
contribute to modifying the cell survival capacity and cells were predominantly CD57+/CD133-. Even the
differentiation status of MDA-MB-231 cells and may CD133+ cells were frequently dual-positive with CD57
correspond to a phenotype linked to carcinogenesis. (CD33+CD57+), not only in the xenograft tumors
The increase in this expression with higher radiation but also in a separate set of patient GBM samples.
dose in the positive CSC population may play a role Mechanistically, we found that CD57+ cells expressed
in the development of secondary tumors, facilitating high levels of self-renewal genes and tend to stay in
ECM degradation by the cells that survive radiation. G0/G1 phases. In conclusion, we showed that invasive
Administration of inhibitors of these MMPs to patients GBM cells are biologically deferent from the matched
undergoing radiotherapy may be useful to avoid the tumor core cells and identified CD57 as a novel stem
radiation-induced development of a more aggressive cell marker that is associated with GBM infiltration.
phenotype that promotes tumor progression. Both Our findings suggest that new anti-invasion therapies
MMP-2 and MMP-9 may be considered novel should target CD57+ cells in addition to CD133+ cells
therapeutic targets in cancer treatment. in GBM.

Key words: Key words:
CSCs, ionizing radiation, MMPs, breast cancer, HDAC CD57, GBM, xenograft

A26 A27
CD57 defines a novel maker of glioblastoma Investigating radiation induced changes
stem cells that have greater invasive in stem cell population of non-small cell
potential than CD133+ tumor cells lung cancer (NSCLC) models following
stereotactic ablative radiotherapy (SABR)
Lin Qi, Yulun Huang, Mari Kogiso, Hua Mao, Holly
Lindsay, Patricia Baxter, Jack Su, Laszlo Perlaky, Ching Charlene Junkin , Victoria Dunne , Gerry Hanna , Kevin
1
1,2
1
Lau, Murali Chintagumpala, Xiao-Nan Li Prise , Karl Butterworth 1
1
Baylor College of Medicine, Houston, USA 1 Queen’s University Belfast, Belfast, UK;
2 Clinicial Oncology, Northern Ireland Cancer Centre, Belfast, UK
Glioblastoma multiforme (GBM) is the most aggressive
and lethal brain tumor that occurs both in children and SABR is emerging as a powerful clinical technique
adults. Diffuse invasion into normal brain tissue is for the treatment of localised and inoperable
one of the important biologic features that make GBM NSCLC. Despite improvements using radical chemo-
refractory to conventional therapies. While existing radiotherapy, overall 5 year survival rates remain low at
studies on GBM invasion are primarily conducted between 7-20%, better strategies are urgently needed
using tumor core tissues from surgical resections, it to improve control rates. Radiotherapy failure can be
is unclear whether unresectable, infiltrative GBM cells attributed to resistance as a result of heterogeneity
would be more informative for studying their invasive within the tumour which may include a sub-population
nature compared to those in the resected tumor cores. of cancer stem cells (CSCs), these may impact the
More importantly, little is known if and which cancer ability of the tumours to recur following radiotherapy.
stem cell populations are driving glioma invasion. To Furthermore, radiation exposure may impact CSC
address these fundamental issues, we utilized our populations causing differentiated cells to acquire
panel of 7 (6 pediatric and 1 adult) patient tumor- stem-like properties or normal stem cells to transform
derived orthotopic xenograft mouse models of GBM to into CSCs due to genetic alteration or changes in the
isolate invasive GBM cells (infiltrating normal mouse normal stem cell microenvironment. The underlying
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Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ November 16, 2016