title: RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis.
abstract: Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non-small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genesTph2,Sspo,Ptprq, andPoleas well as those of the human genesCXCR4,PLLP,TNFSF4,VCAM1,SLC8A2, andSLC7A11were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients.
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan; Department of Respiratory Medicine, Kumamoto University, Kumamoto, Japan.
authors.forename: Ryo
authors.identifier: 0000-0002-2369-2113
authors.initials: R
authors.lastname: Sato
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Teppei
authors.identifier: 0000-0001-5697-788X
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan; Department of Breast Surgical Oncology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Hosonaga
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Oltea
authors.identifier: 0000-0001-5783-1049
authors.initials: O
authors.lastname: Sampetrean
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Ritsuko
authors.identifier: 0000-0001-9740-4607
authors.initials: R
authors.lastname: Harigai
authors.affiliation: The Center for Integrated Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.identifier: 0000-0002-6275-046X
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Koya
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hideyuki
authors.identifier: 0000-0001-7482-5935
authors.initials: H
authors.lastname: Okano
authors.affiliation: Laboratory of Gene Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Jun
authors.identifier: 0000-0001-9915-4090
authors.initials: J
authors.lastname: Kudoh
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hideyuki
authors.identifier: 0000-0001-6610-1902
authors.initials: H
authors.lastname: Saya
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yoshimi
authors.identifier: 0000-0002-2384-1406
authors.initials: Y
authors.lastname: Arima
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D017423:Sequence Analysis, RNA; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins