title: High-resolution imaging mass spectrometry reveals detailed spatial distribution of phosphatidylinositols in human breast cancer.
abstract: High-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is an emerging application for lipid research that provides a comprehensive and detailed spatial distribution of ionized molecules. Recent lipidomic approach has identified several phospholipids and phosphatidylinositols (PIs) are accumulated in breast cancer tissues and are therefore novel biomarker candidates. Because their distribution and significance remain unclear, we investigated the precise spatial distribution of PIs in human breast cancer tissues using high-resolution MALDI IMS. We evaluated tissues from nine human breast cancers and one normal mammary gland by negative ion MALDI IMS at a resolution of 10 μm. We detected 10 PIs with different fatty acid compositions, and their proportions were remarkably variable in the malignant epithelial regions. High-resolution imaging enabled us to discriminate cancer cell clusters from the adjacent stromal tissue within epithelial regions; moreover, this technique revealed that several PIs were specifically localized to cancer cell clusters. These PIs were heterogeneously distributed within cancer cell clusters, allowing us to identify two different populations of cancer cells that predominantly expressed either PI(18:0/18:1) or PI(18:0/20:3). Tracing the expression level of PIs during cancer cell progression suggested that the latter population is associated with the invasion. Our study documents a novel model for phospholipid analysis of breast cancer tissues by using high-resolution MALDI IMS and identifies candidate PIs that can describe a specific phenotype of cancer cells.
authors.affiliation: Department of Breast Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kawashima
authors.forename: Noriko
authors.initials: N
authors.lastname: Iwamoto
authors.forename: Nobuko
authors.initials: N
authors.lastname: Kawaguchi-Sakita
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ueno
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Mikami
authors.forename: Kazuya
authors.initials: K
authors.lastname: Terasawa
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Sato
authors.forename: Koichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Shimizu
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000737:chemistry; D001943:Breast Neoplasms / Q000737:chemistry* / Q000648:ultrastructure; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000648:ultrastructure; D018450:Disease Progression; D004847:Epithelial Cells / Q000737:chemistry; D005227:Fatty Acids / Q000032:analysis; D005260:Female; D005348:Fibrocystic Breast Disease / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010641:Phenotype; D010716:Phosphatidylinositols / Q000032:analysis*; D017698:Postmenopause; D017697:Premenopause; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D017154:Stromal Cells / Q000737:chemistry
chemical_list: D005227:Fatty Acids; D010716:Phosphatidylinositols; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone