cancer-stem-cells-2018-scientifictracks

12 / 38

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
alliedacademies
Page 30
CANCER STEM CELLS AND
ONCOLOGY RESEARCH
11th International Conference on
Journal of Medical Oncology and Therapeutics | Volume 3
Federica Verginelli et al., J Med Oncl Ther 2018, Volume 3
ISOLATION OF CANCER STEM
CELLS FROM CANCER OF
UNKNOWN PRIMARY ORIGIN
(CUP) AND GENERATION OF A
NOVEL IN VIVO MODEL OF EARLY,
SPONTANEOUS AND MULTIPLE
METASTASES BY SUBCUTANEOUS
TRANSPLANTATION
Federica Verginelli, D’Ambrosio Antonio, Carollo Rosachiara,
Benvenuti Silvia, Senetta Rebecca, Pisacane Alberto, Geuna
Elena, Gentile Alessandra, Marsoni Silvia, Balsamo Anton-
ella, Montemurro Filippo, Sapino Anna , Comoglio Paolo M.,
and Boccaccio Carla
Candiolo Cancer Institute, Italy
Cancer of unknown primary origin or CUPs, represent 3-5% of all
cancers with a very poor prognosis (overall survival: 9 months).
Patients display unpredictable and precocious metastatic dissemination
in the absence of a clinically detectable primary lesion. Histologically,
CUPs display mostly epithelial morphology but, invariably, they lack
expression of lineage markers that allow unambiguous identification
of the tissue of origin. Today many efforts are aimed to develop new
molecular diagnostic tools to predict the primary tissue and guide to
a more rational therapeutic choice. However, the aberrant molecular
mechanisms underlying CUP pathogenesis are largely obscure. Here,
we show for the first time the isolation and the extensive in vitro and
in vivo characterization of cancer stem cells isolated from CUPs, as
cultures named “agnospheres”. Specifically, agnospheres are able to
grow in suspension and in the absence of growth factors, they express
well-known stem cell markers and are endowed with self-renewal ability
and long term propagation in vitro. They repopulate a tumor when
transplanted subcutis in immunocompromised mice at very low number
(i.e. as few as 10 cells, stem cells frequency: 5-15%). Most importantly,
after subcutaneous transplantation, agnospheres recapitulate the whole
metastatic cascade, generating metastases in multiple organs (lung,
lymph nodes, thymus...) within a month (estimated metastatic stem
cell frequency: 1-2%). For the first time to our knowledge, cancer stem
cells have been isolated from CUPs, and phenotypically and functionally
characterized. We generated a new cancer stem cell model endowed
with extremely high tumor-initiating ability and impressive precocious
metastogenic potential in different organs. Agnospheres may represent
Federica Verginelli has accomplished her PhD
in Cellular and Molecular Biology at the Tor Ver-
gata University in Rome (Italy), and a 4-years
post-doc at the Montreal Neurological Institute
(Canada). She is now research associate at the
Candiolo Cancer Institute (Italy). She is author
of 10 publications that have been cited 297
times, and her publication H-Index is 8.
BIOGRAPHY
an unprecedented tool for investigating the
molecular mechanisms responsible for the
metastatic process in general, and to assess
the anti-metastatic effect of approved or new
therapeutic compounds.