title: Proteomic comparison of mcf-7 tumoursphere and monolayer cultures.
abstract: Breast cancer is a heterogeneous disease, composed of tumour cells with differing gene expressions and phenotypes. Very few antigens have been identified and a better understanding of tumour initiating-cells as targets for therapy is critically needed. Recently, a rare subpopulation of cells within tumours has been described with the ability to: (i) initiate and sustain tumour growth; (ii) resist traditional therapies and allow for secondary tumour dissemination; and (iii) display some of the characteristics of stem cells such as self-renewal. These cells are termed tumour-initiating cells or cancer stem cells, or alternatively, in the case of breast cancer, breast cancer stem cells. Previous studies have demonstrated that breast cancer stem cells can be enriched for in "tumoursphere" culture. Proteomics represents a novel way to investigate protein expression between cells. We hypothesise that characterisation of the proteome of the breast cancer line MCF-7 tumourspheres compared to adherent/differentiated cells identifies proteins of novel interest for further isolating or targeting breast cancer stem cells. We present evidence that: (i) the proteome of adherent cells is different to the proteome of cells grown in sphere medium from either early passage (passage 2) or late passage (passage 5) spheres; (ii) that spheres are enriched in expression of a variety of tumour-relevant proteins (including MUC1 and Galectin-3); and (iii) that targeting of one of these identified proteins (galectin-3) using an inhibitor (N-acetyllactosamine) decreases sphere formation/self-renewal of MCF-7 cancer stem cells in vitro and tumourigenicity in vivo. Hence, proteomic analysis of tumourspheres may find use in identifying novel targets for future therapy. The therapeutic targeting of breast cancer stem cells, a highly clinically relevant sub-population of tumour cells, has the potential to eliminate residual disease and may become an important component of a multi-modality treatment of cancer.
authors.affiliation: School of Biomolecular and Physical Sciences, Griffith University, Brisbane, Queensland, Australia.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Morrison
authors.forename: Marcus L
authors.initials: ML
authors.lastname: Hastie
authors.forename: Yadveer S
authors.initials: YS
authors.lastname: Grewal
authors.forename: Zara C
authors.initials: ZC
authors.lastname: Bruce
authors.forename: Chris
authors.initials: C
authors.lastname: Schmidt
authors.forename: Brent A
authors.initials: BA
authors.lastname: Reynolds
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Gorman
authors.forename: J Alejandro
authors.initials: JA
authors.lastname: Lopez
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D005260:Female; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism; D010641:Phenotype; D020543:Proteome; D040901:Proteomics; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured
chemical_list: D037483:Galectin 1; D037502:Galectin 3; D018396:Mucin-1; D020543:Proteome