title: Extracellular matrix constituents interfere with Newcastle disease virus spread in solid tissue and diminish its potential oncolytic activity.
abstract: Advanced melanoma cells, characterized by resistance to chemotherapy, have been shown to be highly sensitive to oncolysis by Newcastle disease virus (NDV). In the present study, we investigated the capacity of NDV to specifically infect and spread into solid tissues of human melanoma and lung carcinoma, in vivo and ex vivo. For this purpose a new model of SCID-beige mice implanted with human melanoma was developed. Surprisingly, the replication competent NDV-MTH and the attenuated, single-cycle replication NDV-HUJ strains, demonstrated a similar oncolytic activity in the melanoma-implanted mice. Further, ex vivo analysis, using organ cultures derived from the melanoma tissues indicated a limited spread of the two NDV strains in the tissue. Extracellular matrix (ECM) molecules, notably heparin sulfate and collagen, were found to limit viral spread in the tissue. This observation was validated with yet another solid tumour of human lung carcinoma. Taken together, the results indicate that the ECM acts as a barrier to virus spread within solid tumour tissues and that this restriction must be overcome to achieve effective oncolysis with NDV.
authors.affiliation: Department of Biochemistry, the Chanock Center for Virology, IMRIC, Hadassah Medical Center-Hebrew University, Jerusalem 91120, Israel.
authors.forename: Barak
authors.initials: B
authors.lastname: Yaacov
authors.affiliation: Department of Hematology, Hadassah Medical Center-Hebrew University, Jerusalem 91120, Israel.
authors.forename: Itay
authors.initials: I
authors.lastname: Lazar
authors.affiliation: Department of Biochemistry, the Chanock Center for Virology, IMRIC, Hadassah Medical Center-Hebrew University, Jerusalem 91120, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Tayeb
authors.affiliation: Department of Hematology, Hadassah Medical Center-Hebrew University, Jerusalem 91120, Israel.
authors.forename: Sivan
authors.initials: S
authors.lastname: Frank
authors.affiliation: Department of Cardiothoracic Surgery, Hadassah Medical Center-Hebrew University, Jerusalem 91120, Israel.
authors.forename: Uzi
authors.initials: U
authors.lastname: Izhar
authors.affiliation: Department of Oncology, Hadassah Medical Center-Hebrew University, Jerusalem 91120, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Lotem
authors.affiliation: Department of Hematology, Hadassah Medical Center-Hebrew University, Jerusalem 91120, Israel.
authors.forename: Riki
authors.initials: R
authors.lastname: Perlman
authors.affiliation: Department of Hematology, Hadassah Medical Center-Hebrew University, Jerusalem 91120, Israel.
authors.forename: Dina
authors.initials: D
authors.lastname: Ben-Yehuda
authors.affiliation: Department of Biochemistry, the Chanock Center for Virology, IMRIC, Hadassah Medical Center-Hebrew University, Jerusalem 91120, Israel.
authors.forename: Zichria
authors.initials: Z
authors.lastname: Zakay-Rones
authors.affiliation: Department of Biochemistry, the Chanock Center for Virology, IMRIC, Hadassah Medical Center-Hebrew University, Jerusalem 91120, Israel.
authors.forename: Amos
authors.initials: A
authors.lastname: Panet
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000378:metabolism* / Q000821:virology*; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000821:virology*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009522:Newcastle disease virus / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D046509:Tissue Culture Techniques; D014779:Virus Replication