title: Wharton's jelly mesenchymal stromal cells have contrasting effects on proliferation and phenotype of cancer stem cells from different subtypes of lung cancer.
abstract: Studies on the role of multipotent mesenchymal stromal cells (MSC) on tumor growth have reported both a tumor promoting and a suppressive effect. The aim of the present study was to determine the effect of MSC isolated from Wharton's jelly of umbilical cord (WJMSC) on lung cancer stem cells (LCSC) derived from human lung tumors: two adenocarcinomas (AC) and two squamous cell carcinomas (SCC). LCSC derived from SCC and AC expressed, to varying extents, the more relevant stem cell markers. The effect of WJMSC on LCSC was investigated in vitro using conditioned medium (WJ-CM): a proliferation increase in AC-LCSC was observed, with an increase in the ALDH+ and in the CD133+ cell population. By contrast, WJ-CM hampered the growth of SCC-LCSC, with an increase in the pre-G1 phase indicating the induction of apoptosis. Furthermore, the ALDH+ and CD133+ population was also reduced. In vivo, subcutaneous co-transplantation of AC-LCSC/WJMSC generated larger tumors than AC-LCSC alone, characterized by an increased percentage of CD133+ and CD166+ cells. By contrast, co-transplantation of WJMSC and SCC-LCSC did not affect the tumor size. Our results strongly suggest that WJMSC exert, both in vitro and in vivo, contrasting effects on LCSC derived from different lung tumor subtypes.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. Electronic address: francesca.vulcano@iss.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Vulcano
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. Electronic address: luisa.milazzo@iss.it.
authors.forename: Luisa
authors.initials: L
authors.lastname: Milazzo
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Italy. Electronic address: carmela.ciccarelli@univaq.it.
authors.forename: Carmela
authors.initials: C
authors.lastname: Ciccarelli
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. Electronic address: adriana.eramo@iss.it.
authors.forename: Adriana
authors.initials: A
authors.lastname: Eramo
authors.affiliation: Regina Elena National Cancer Institute, Rome, Italy. Electronic address: giovanni.sette@gmail.com.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sette
authors.affiliation: Faculty of Veterinary Medicine, University of Teramo, Italy. Electronic address: amauro@unite.it.
authors.forename: Annunziata
authors.initials: A
authors.lastname: Mauro
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. Electronic address: giampiero.macioce@iss.it.
authors.forename: Giampiero
authors.initials: G
authors.lastname: Macioce
authors.affiliation: Experimental Animal Welfare Sector of the Istituto Superiore di Sanità, Rome, Italy. Electronic address: andrea.martinelli@iss.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Martinelli
authors.affiliation: Department of Gynecology, Obstetrics and Urological Sciences, Sapienza University of Rome, Italy. Electronic address: renato.latorre@uniroma1.it.
authors.forename: Renato
authors.initials: R
authors.lastname: La Torre
authors.affiliation: Institute of Cell Biology and Neurobiology, National Research Council, Rome, Italy. Electronic address: patrizia.casalbore@cnr.it.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Casalbore
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. Electronic address: jane.hassan@iss.it.
authors.forename: Hamisa Jane
authors.initials: HJ
authors.lastname: Hassan
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. Electronic address: adele.giampaolo@iss.it.
authors.forename: Adele
authors.initials: A
authors.lastname: Giampaolo
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000145:classification* / Q000473:pathology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010641:Phenotype; D040521:Subcutaneous Tissue / Q000473:pathology; D059631:Wharton Jelly / Q000166:cytology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D017077:Culture Media, Conditioned
keywords: ALDH; CD133; Lung cancer stem cells; Mesenchymal stromal cells; Tumor xenografts; Wharton's jelly