title: Color-Coded Imaging of Breast Cancer Metastatic Niche Formation in Nude Mice.
abstract: We report here a color-coded imaging model in which metastatic niches in the lung and liver of breast cancer can be identified. The transgenic green fluorescent protein (GFP)-expressing nude mouse was used as the host. The GFP nude mouse expresses GFP in all organs. However, GFP expression is dim in the liver parenchymal cells. Mouse mammary tumor cells (MMT 060562) (MMT), expressing red fluorescent protein (RFP), were injected in the tail vein of GFP nude mice to produce experimental lung metastasis and in the spleen of GFP nude mice to establish a liver metastasis model. Niche formation in the lung and liver metastasis was observed using very high resolution imaging systems. In the lung, GFP host-mouse cells accumulated around as few as a single MMT-RFP cell. In addition, GFP host cells were observed to form circle-shaped niches in the lung even without RFP cancer cells, which was possibly a niche in which future metastasis could be formed. In the liver, as with the lung, GFP host cells could form circle-shaped niches. Liver and lung metastases were removed surgically and cultured in vitro. MMT-RFP cells and GFP host cells resembling cancer-associated fibroblasts (CAFs) were observed interacting, suggesting that CAFs could serve as a metastatic niche.
authors.affiliation: Gifu University, Graduate School of Medicine, Gifu, Japan.|AntiCancer, Inc., San Diego, California.|Department of Surgery, University of California, San Diego, California.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suetsugu
authors.affiliation: AntiCancer, Inc., San Diego, California.|Department of Surgery, University of California, San Diego, California.
authors.forename: Masashi
authors.initials: M
authors.lastname: Momiyama
authors.affiliation: AntiCancer, Inc., San Diego, California.|Department of Surgery, University of California, San Diego, California.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hiroshima
authors.affiliation: Gifu University, Graduate School of Medicine, Gifu, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Gifu University, Graduate School of Medicine, Gifu, Japan.
authors.forename: Shigetoyo
authors.initials: S
authors.lastname: Saji
authors.affiliation: Gifu University, Graduate School of Medicine, Gifu, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
authors.affiliation: Department of Surgery, University of California, San Diego, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
authors.affiliation: AntiCancer, Inc., San Diego, California.|Department of Surgery, University of California, San Diego, California.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D009362:Neoplasm Metastasis; D059016:Tumor Microenvironment / Q000235:genetics*; D000097573:Red Fluorescent Protein
chemical_list: D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein
keywords: BREAST CANCER; CANCER-ASSOCIATED FIBROBLASTS; COLOR-CODED IMAGING; GFP; LIVER; LUNG; METASTATIS; NICHE; RFP