Parvovirus H-1 induces cytopathic effects in breast carcinoma-derived cultures.
Parvovirus H-1 (H-1 PV) preferentially replicates in malignant cells resulting in their death by cytolysis. It has often been considered a potential candidate for use in novel anticancer therapy. To evaluate its potential in a model of natural tumors, we assayed in vitro the effect exerted by H-1 PV on short-term cultures derived from breast tumor samples freshly excised from patients. Our results show that H-1 PV effectively kills tumor-derived cells, whereas normal tissue-derived cells showed no H-1 PV-induced cytopathic effects (CPE). We also determined that the H-1 PV sensitivity (up to 67% sensitive cultures) is related with the quantities of virus assayed. We further examined the expression and phosphorylation state of the parvoviral nonstructural protein 1 (NS1), known to be associated with parvoviruses-induced CPE. Both appear to be impaired in normal tissue-derived cells and resistant cultures. Finally, we show that H-1 PV sensitivity in cultures correlates significantly with higher tumor grades (Nottingham combined histologic grade 2 or 3). This report confirms that H-1 PV can efficiently induce CPE in primary breast tumor cells in vitro. It identifies tumor characteristics representing potential criteria for recruiting patients for clinical evaluation of H-1 PV antitumor effects.
Muharram
Ghaffar
G
CNRS, UMR 8161, Institut de Biologie de Lille, Lille cedex, France. ghaffar.muharram@ibl.fr
Le Rhun
Emilie
E
Loison
Ingrid
I
Wizla
Pierre
P
Richard
Audrey
A
Martin
Nathalie
N
Roussel
Annie
A
Begue
Agnes
A
Devos
Patrick
P
Baranzelli
Marie-Christine
MC
Bonneterre
Jacques
J
Caillet-Fauquet
Perrine
P
Stehelin
Dominique
D
D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy / Q000821:virology*; D002478:Cells, Cultured; D005260:Female; D052661:H-1 parvovirus; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D050130:Oncolytic Virotherapy / Q000379:methods*; D023041:Xenograft Model Antitumor Assays