title: A mathematical-biological joint effort to investigate the tumor-initiating ability of Cancer Stem Cells.
abstract: The involvement of Cancer Stem Cells (CSCs) in tumor progression and tumor recurrence is one of the most studied subjects in current cancer research. The CSC hypothesis states that cancer cell populations are characterized by a hierarchical structure that affects cancer progression. Due to the complex dynamics involving CSCs and the other cancer cell subpopulations, a robust theory explaining their action has not been established yet. Some indications can be obtained by combining mathematical modeling and experimental data to understand tumor dynamics and to generate new experimental hypotheses. Here, we present a model describing the initial phase of ErbB2(+) mammary cancer progression, which arises from a joint effort combing mathematical modeling and cancer biology. The proposed model represents a new approach to investigate the CSC-driven tumorigenesis and to analyze the relations among crucial events involving cancer cell subpopulations. Using in vivo and in vitro data we tuned the model to reproduce the initial dynamics of cancer growth, and we used its solution to characterize observed cancer progression with respect to mutual CSC and progenitor cell variation. The model was also used to investigate which association occurs among cell phenotypes when specific cell markers are considered. Finally, we found various correlations among model parameters which cannot be directly inferred from the available biological data and these dependencies were used to characterize the dynamics of cancer subpopulations during the initial phase of ErbB2+ mammary cancer progression.
authors.affiliation: Department of Computer Science, University of Torino, Torino, Italy; Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fornari
authors.affiliation: Department of Computer Science, University of Torino, Torino, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Beccuti
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Lanzardo
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Conti
authors.affiliation: Department of Computer Science, University of Torino, Torino, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Balbo
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy.
authors.forename: Raffaele A
authors.initials: RA
authors.lastname: Calogero
authors.affiliation: Department of Computer Science, University of Torino, Torino, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cordero
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051927:CD24 Antigen / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D015233:Models, Statistical; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology; D016042:Transplantation, Heterotopic
chemical_list: D015415:Biomarkers; D051927:CD24 Antigen; D018960:Hyaluronan Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human