title: Absence of endothelial cells, central necrosis, and fibrosis are associated with aggressive inflammatory breast cancer.
abstract: We recently established a new human inflammatory breast cancer (IBC) xenograft (WIBC-9) originating from a patient with IBC. The graft was transplantable in BALB/c nude and severe combined immunodeficient (SCID) mice. WIBC-9 was frequently accompanied by lung metastasis and exhibited erythema of the overlying skin, reflecting its human counterpart. Histological study of the original tumor and WIBC-9 revealed invasive ductal carcinoma with a hypervascular structure of solid nests and marked lymphatic permeation in the overlying dermis. In the central part of the solid nests, absence of endothelial cells, central necrosis, and fibrosis were observed. In vitro, WIBC-9 formed tube-like structures and loops, reflecting its in vivo feature and its human counterpart. WIBC-9 exhibited aneuploidy, ErbB-2 gene amplification, and an absence of estrogen receptor and progesterone receptor, which is consistent with IBC. Comparative studies of WIBC-9, three established non-IBC xenografts, and a human breast cancer cell line (SK-BR3) by reverse transcription-PCR, ELISA, and immunohistochemistry indicated that certain human genes (interleukin 8, vascular epidermal growth factor, basic fibroblast growth factor, angiopoietin 13, Flt-1, Tie-2, and Tie-1) and certain murine genes (integrin alpha(v)beta3, flt-1, tie-2, vascular epidermal growth factor, and CD31) were overexpressed in exposure to tumor cells. The molecular basis and these unique histological features may be associated with aggressive IBC on angiogenic and nonangiogenic pathways.
authors.affiliation: Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shirakawa
authors.forename: H
authors.initials: H
authors.lastname: Tsuda
authors.forename: Y
authors.initials: Y
authors.lastname: Heike
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: R
authors.initials: R
authors.lastname: Asada
authors.forename: M
authors.initials: M
authors.lastname: Inomata
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.forename: F
authors.initials: F
authors.lastname: Kasumi
authors.forename: M
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: T
authors.initials: T
authors.lastname: Iwanaga
authors.forename: F
authors.initials: F
authors.lastname: Konishi
authors.forename: M
authors.initials: M
authors.lastname: Terada
authors.forename: H
authors.initials: H
authors.lastname: Wakasugi
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005355:Fibrosis; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008854:Microscopy, Electron; D008875:Middle Aged; D009336:Necrosis; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D042787:Receptor, TIE-2; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D043925:Angiogenesis Inducing Agents; D015820:Cadherins; D016207:Cytokines; D016023:Integrins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; D040262:Receptors, Vascular Endothelial Growth Factor