Therapeutic potential of replication-selective oncolytic adenoviruses on cells from familial and sporadic desmoid tumors.
OBJECTIVE
Constitutive activation of the Wnt signaling pathway is a hallmark of many cancers and has been associated with familial and sporadic desmoid tumors. The aim of the present study is to assess the therapeutic potential of oncolytic adenoviruses selectively replicating in cells in which the Wnt signaling pathway is active on primary cells from desmoid tumors.


METHODS
Primary cells extracted from familial (n = 3) or sporadic (n = 3) desmoid tumors were cultured short term. Cancer cell survival and viral replication were measured in vitro upon infection with two different oncolytic adenoviruses targeting a constitutive activation of the Wnt signaling pathway. Adenoviral infectivity was also assessed.


RESULTS
Although cells extracted from one sporadic desmoid tumor responded very well to the oncolytic action of the adenoviruses (<20% of viable cells upon infection at a multiplicity of infection of 10), cells from two tumor samples were totally resistant to the viral action. Cells from the remaining samples showed intermediate sensitivity to the oncolytic viruses. These effects were correlated to the level of infectivity of the cells. Finally, in responder cells, evidences of viral replication was observed.


CONCLUSIONS
Our experimental data suggest that the response of desmoid tumor cells to oncolytic adenovirus is neither correlated to the type of mutation activating the Wnt signaling pathway nor to the familial or sporadic nature of the tumor. In addition, they highlight the variability of infectivity of individual tumors and predict a great variability in the response to oncolytic adenoviruses.
Peerlinck
Inge
I
Institute of Cancer and the CR-UK Clinical Centre, Barts and The London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom.
Amini-Nik
Saeid
S
Phillips
Robin K
RK
Iggo
Richard
R
Lemoine
Nicholas R
NR
Tejpar
Sabine
S
Vassaux
Georges
G
D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology*; D045744:Cell Line, Tumor; D002469:Cell Separation; D004770:Enterovirus / Q000378:metabolism; D018222:Desmoid Tumors / Q000378:metabolism* / Q000628:therapy*; D005434:Flow Cytometry; D006801:Humans; D009369:Neoplasms / Q000378:metabolism; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics* / Q000502:physiology*; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D019076:Transgenes; D014779:Virus Replication