title: Preventive cancer stem cell-based vaccination reduces liver metastasis development in a rat colon carcinoma syngeneic model.
abstract: Cancer stem cells (CSCs) represent a minor population of self-renewing cancer cells that fuel tumor growth. As CSCs are generally spared by conventional treatments, this population is likely to be responsible for relapses that are observed in most cancers. In this work, we analyzed the preventive efficiency of a CSC-based vaccine on the development of liver metastasis from colon cancer in a syngeneic rat model. We isolated a CSC-enriched population from the rat PROb colon carcinoma cell line on the basis of the expression of the aldehyde dehydrogenase-1 (ALDH1) marker. Comparative analysis of vaccines containing lysates of PROb or ALDH(high) cells by mass spectrometry identifies four proteins specifically expressed in the CSC subpopulation. The expression of two of them (heat shock protein 27-kDa and aldose reductase) is already known to be associated with treatment resistance and poor prognosis in colon cancer. Preventive intraperitoneal administration of vaccines was then performed before the intrahepatic injection of PROb cancer cells. While no significant difference in tumor occurrence was observed between control and PROb-vaccinated groups, 50% of the CSC-based vaccinated animals became resistant to tumor development. In addition, CSC-based vaccination induced a 99.5% reduction in tumor volume compared to the control group. To our knowledge, this study constitutes the first work analyzing the potential of a CSC-based vaccination to prevent liver metastasis development. Our data demonstrate that a CSC-based vaccine reduces efficiently both tumor volume and occurrence in a rat colon carcinoma syngeneic model.
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Sonia
authors.initials: S
authors.lastname: Duarte
authors.forename: David
authors.initials: D
authors.lastname: Momier
authors.forename: Patrick
authors.initials: P
authors.lastname: Baqué
authors.forename: Vincent
authors.initials: V
authors.lastname: Casanova
authors.forename: Agnès
authors.initials: A
authors.lastname: Loubat
authors.forename: Michel
authors.initials: M
authors.lastname: Samson
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Guigonis
authors.forename: Pascal
authors.initials: P
authors.lastname: Staccini
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Saint-Paul
authors.forename: Maria Pedroso
authors.initials: MP
authors.lastname: De Lima
authors.forename: Georges F
authors.initials: GF
authors.lastname: Carle
authors.forename: Valérie
authors.initials: V
authors.lastname: Pierrefite-Carle
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology*; D015197:Carcinogenicity Tests; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary*; D008297:Male; D014411:Neoplastic Stem Cells / Q000201:enzymology / Q000276:immunology*; D051381:Rats; D050697:Retinal Dehydrogenase / Q000096:biosynthesis
chemical_list: D019496:Cancer Vaccines; D000080924:Aldehyde Dehydrogenase 1 Family; C523119:Aldh1a1 protein, rat; D050697:Retinal Dehydrogenase