title: Different molecular profiles are associated with breast cancer cell homing compared with colonisation of bone: evidence using a novel bone-seeking cell line.
abstract: Advanced breast cancer is associated with the development of incurable bone metastasis. The two key processes involved, tumour cell homing to and subsequent colonisation of bone, remain to be clearly defined. Genetic studies have indicated that different genes facilitate homing and colonisation of secondary sites. To identify specific changes in gene and protein expression associated with bone-homing or colonisation, we have developed a novel bone-seeking clone of MDA-MB-231 breast cancer cells that exclusively forms tumours in long bones following i.v. injection in nude mice. Bone-homing cells were indistinguishable from parental cells in terms of growth rate in vitro and when grown subcutaneously in vivo. Only bone-homing ability differed between the lines; once established in bone, tumours from both lines displayed similar rates of progression and caused the same extent of lytic bone disease. By comparing the molecular profile of a panel of metastasis-associated genes, we have identified differential expression profiles associated with bone-homing or colonisation. Bone-homing cells had decreased expression of the cell adhesion molecule fibronectin and the migration and calcium signal binding protein S100A4, in addition to increased expression of interleukin 1B. Bone colonisation was associated with increased fibronectin and upregulation of molecules influencing signal transduction pathways and breakdown of extracellular matrix, including hRAS and matrix metalloproteinase 9. Our data support the hypothesis that during early stages of breast cancer bone metastasis, a specific set of genes are altered to facilitate bone-homing, and that disruption of these may be required for effective therapeutic targeting of this process.
authors.affiliation: Academic Unit of Clinical Oncology, Cancer Research UK (CR-UK), and Yorkshire Cancer Research (YCR) Sheffield Cancer Research Centre Academic Unit of Pathology, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK Leeds Institute of Molecular Medicine, CR-UK Cancer Research Centre, University of Leeds, Leeds, UK.
authors.forename: Faith
authors.initials: F
authors.lastname: Nutter
authors.forename: Ingunn
authors.initials: I
authors.lastname: Holen
authors.forename: Hannah K
authors.initials: HK
authors.lastname: Brown
authors.forename: Simon S
authors.initials: SS
authors.lastname: Cross
authors.forename: C Alyson
authors.initials: CA
authors.lastname: Evans
authors.forename: Matthew
authors.initials: M
authors.lastname: Walker
authors.forename: Robert E
authors.initials: RE
authors.lastname: Coleman
authors.forename: Jules A
authors.initials: JA
authors.lastname: Westbrook
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Selby
authors.forename: Janet E
authors.initials: JE
authors.lastname: Brown
authors.forename: Penelope D
authors.initials: PD
authors.lastname: Ottewell
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude
chemical_list: D053583:Interleukin-1beta
keywords: bone; breast; metastasis