cancer-stem-cells-2018-keynote

allied

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CANCER STEM CELLS AND

ONCOLOGY RESEARCH

International Conference on

J u n e 1 1 - 1 3 , 2 0 1 8 | D u b l i n , I r e l a n d

Journal of Medical Oncology and Therapeutics

Volume 3

Page 18

Note:

dentification of cancer stem cells (CSC) in solid tumours – with

self-renewal, multipotency, tumorigenesis, and therapy resistance

capacities – has opened path to new targeting therapeutic approaches.

However, CSC targeting alone might not be sufficient to eradicate a

tumour. Indeed, recent studies showed that cancer cells are plastic,

and conventional therapies, such as radiotherapy, can lead to cancer

cells (non-CSC) reprogramming into iCSC (induced-CSC). The goal

of our work is to identify the molecular mechanisms responsible

for treatment-induced CSC emergence. First, we have shown that

conditioned media from irradiated non-CSC is sufficient to induce iCSC

reprogramming. These results suggest that cell plasticity might be

actively regulated by diffusible factors secreted by irradiated cells. By

using proteins arrays and ELISA, we demonstrated that the secretion

of a specific cocktail of chemokines is induced by ionizing radiation,

such as CXCL1 and CCL5. Interestingly, recombinant CXCL1 and CCL5

treatments increase the sphere forming capacity (SFC) of isolated non-

CSC treated population. Concomitantly, treatment with neutralizing

antibodies targeting CXCL1 and CCL5 leads to a decreased CSC number

(ALDH+ cells). Most importantly, treatment with neutralising antibodies

through radiation treatment of xenograft in SCID mice double the

survival time of the mice. Preclinical study show predictive value of

CXCL1 and CCL5 expression. We also studied the expression of the

corresponding chemokines receptors, by flow cytometry. First, we saw

that reprogrammable ALDH- cells are enriched for CXCL1 and CCL5

receptors expressing cells compare to unsorted population or ALDH+

population (CSC). We analysed the reprogramming potential of isolated

ALDH-/receptor-positive cells versus ALDH-/receptor-negative cells.

The ALDH-/receptor-positive-derived cell population is more able to

form spheres and overcomes the receptor-negative-derived population

when the two populations are mixed and tested for their sphere forming

capacity. The use of pharmacological inhibitors against the receptors

induce a slight decrease of CSC. Taken together, our results indicate

the involvement of chemokines, in particular CXCL1 and CCL5, in the

reprogramming mechanism.

Biography

Chann Lagadec has spent five years as a Post-

doctoral fellowship in Dr. Pajonk’lab, a pioneer in

CSC research field. Within the time at UCLA in the

Radiation Oncology Department, he got trained in

CSC and was the first to demonstrate the pheno-

type plasticity of CSC induced by radiation treat-

ment. Since 2012, he set up his own team in the

INSERM U908 lab in Lille, France, where he stud-

ies the molecular mechanisms involved in the

reprogramming process. He develops molecular

tools and an animal model to track and charac-

terize CSC and iCSC. His domain of interest en-

larges recently to understand the potential role of

reprogramming in tumor dormancy andmetasta-

sis development.

chann.lagadec@inserm.fr

INFLAMMATORY CYTOKINES,

INDUCED BY IONIZING RADIATION,

REPROGRAM NON-TUMORIGENIC

CANCER CELLS INTO CANCER

STEM CELLS IN BREAST CANCER

Chann Lagadec

INSERM, France

Chann Lagadec, J Med Oncl Ther 2018, Volume 3