title: In vivopotential of recombinant granulysin against human tumors.
abstract: 9 kDa granulysin is a protein present in the granules of human CTL and NK cells, with cytolytic activity against microbes and tumors. Previous work from our group demonstrated that this granulysin isoform induced apoptosisin vitroon hematological tumor cells and on primary tumor cells from B-CLL patients. In the present work, recombinant 9 kDa granulysin was used as an anti-tumoral agent to study itsin vivoeffect on tumor development in athymic "nude" mice models bearing human breast adenocarcinoma MDA-MB-231 or multiple myeloma NCI-H929-derived xenografts. Granulysin prevented thein vivodevelopment of detectable MDA-MB-231-derived tumors. In addition, recombinant granulysin was able to completely eradicate NCI-H929-derived tumors. All granulysin-treated tumors exhibited signs of apoptosis induction and an increased NK cell infiltration inside the tumor tissue comparing to control ones. Moreover, noin vivodeleterious effects of the recombinant 9 kDa granulysin doses used in this study were observed on the skin or on the internal organs of the animals. In conclusion, granulysin was able to inhibit the progression of MDA-MB-231-derived xenografts and also to eradicate multiple myeloma NCI-H929-derived xenografts. This work opens the door to the initiation of preclinical and possibly clinical studies for the use of 9 kDa granulysin as a new anti-tumoral treatment.
authors.affiliation: Department of Biochemistry and Molecular and Cell Biology; Apoptosis Immunity & Cancer Group; Faculty of Sciences; University of Zaragoza and Aragón Health Research Institute ; Zaragoza, Spain.
authors.forename: Sameer
authors.initials: S
authors.lastname: Al-Wasaby
authors.affiliation: Department of Biochemistry and Molecular and Cell Biology; Apoptosis Immunity & Cancer Group; Faculty of Sciences; University of Zaragoza and Aragón Health Research Institute ; Zaragoza, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: de Miguel
authors.affiliation: Department of Biochemistry and Molecular and Cell Biology; Apoptosis Immunity & Cancer Group; Faculty of Sciences; University of Zaragoza and Aragón Health Research Institute ; Zaragoza, Spain.
authors.forename: Adriana
authors.initials: A
authors.lastname: Aporta
authors.affiliation: Department of Biochemistry and Molecular and Cell Biology; Apoptosis Immunity & Cancer Group; Faculty of Sciences; University of Zaragoza and Aragón Health Research Institute ; Zaragoza, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Naval
authors.affiliation: Department of Human Anatomy and Histology; Faculty of Medicine; University of Zaragoza ; Zaragoza, Spain ; These authors share senior authorship.
authors.forename: Blanca
authors.initials: B
authors.lastname: Conde
authors.affiliation: Department of Biochemistry and Molecular and Cell Biology; Apoptosis Immunity & Cancer Group; Faculty of Sciences; University of Zaragoza and Aragón Health Research Institute ; Zaragoza, Spain ; Nanoscience Institute of Aragon ; Zaragoza, Spain ; These authors share senior authorship.
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Lostao
authors.affiliation: Department of Biochemistry and Molecular and Cell Biology; Apoptosis Immunity & Cancer Group; Faculty of Sciences; University of Zaragoza and Aragón Health Research Institute ; Zaragoza, Spain ; These authors share senior authorship.
authors.forename: Alberto
authors.initials: A
authors.lastname: Anel
keywords: apoptosis; athymic mice; granulysin; mammary adenocarcinoma; multiple myeloma