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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

allied

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Page 30

CANCER STEM CELLS AND

ONCOLOGY RESEARCH

11

th

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

C

ancer 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.

federica.verginelli@ircc.it

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.