title: Growth and metastatic behavior of molecularly well-characterized human breast cancer cell lines in mice.
abstract: Breast cancer (BC) is a disease with intra- and inter-tumor heterogeneity, and models representing the complete variety of clinical BC phenotypes are not available. We explored the tumor growth potential and metastatic behavior of human BC cell lines and determined whether these cell lines can recapitulate subtype-related biological characteristics of tumors. Eighteen human BC cell lines were implanted under the mammary fat pad of nude mice. Subtype-specific differences in tumor growth, metastatic ability to distant sites, and tumor-related survival of mice were recorded. Eighty-nine percent of the cell lines gave rise to xenografts of which 56 % showed metastasis to distant sites. A clear difference was observed in growth of xenografts from cell lines of different molecular subtypes (P = 0.001; Kruskal-Wallis test). Mice bearing the basal-like and the normal-like xenografts showed poor tumor-related survival (HR: 10.50; P = 0.002 and HR: 9.89; P = 0.003, respectively) compared with those bearing the ERBB2-positive xenografts, which had the longest survival. Subtype-specific metastasis to distant sites between xenografts was not however observed. Comparable to clinical behavior in humans, we observed that the basal-like and the normal-like cell lines grew more aggressively in mice than the cell lines of other molecular subtypes. However, in contrast to clinical findings, we observed no relationships between intrinsic subtype and preferences for site of relapse. Importantly, we have established xenograft models from 16 phenotypically and molecularly diverse human BC cell lines, which can be exploited as useful tools to perform functional studies and screening of interfering drugs.
authors.affiliation: Department of Medical Oncology and Cancer Genomics Centre, Erasmus University Medical Center - Daniel den Hoed Cancer Center, 3000 CA, Rotterdam, The Netherlands, m.riaz@erasmusmc.nl.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Riaz
authors.forename: Buddy
authors.initials: B
authors.lastname: Setyono-Han
authors.forename: Mieke A
authors.initials: MA
authors.lastname: Timmermans
authors.forename: Anita M
authors.initials: AM
authors.lastname: Trapman
authors.forename: Joan
authors.initials: J
authors.lastname: Bolt-de Vries
authors.forename: Antoinette
authors.initials: A
authors.lastname: Hollestelle
authors.forename: Roel C
authors.initials: RC
authors.lastname: Janssens
authors.forename: Maxime P
authors.initials: MP
authors.lastname: Look
authors.forename: Mieke
authors.initials: M
authors.lastname: Schutte
authors.forename: John A
authors.initials: JA
authors.lastname: Foekens
authors.forename: John W M
authors.initials: JW
authors.lastname: Martens
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D014183:Transplantation, Heterologous