title: Serum ANGPTL2 levels reflect clinical features of breast cancer patients: implications for the pathogenesis of breast cancer metastasis.
abstract: BACKGROUND
  Breast cancer is a leading cause of cancer-related death in women worldwide, and its metastasis is a major cause of disease mortality. Therefore, identification of the mechanisms underlying breast cancer metastasis is crucial for the development of therapeutic and diagnostic strategies. Our recent study of immunodeficient female mice transplanted with MDA-MB231 breast cancer cells demonstrated that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) accelerates metastasis through both increasing tumor cell migration in an autocrine/paracrine manner, and enhancing tumor angiogenesis. To determine whether ANGPTL2 contributes to its clinical pathogenesis, we asked whether serum ANGPTL2 levels reflect the clinical features of breast cancer progression.
  
  
  METHODS
  We monitored the levels of secreted ANGPTL2 in supernatants of cultured proliferating MDA-MB231 cells. We also determined whether the circulating ANGPTL2 levels were positively correlated with cancer progression in an in vivo breast cancer xenograft model using MDA-MB231 cells. Finally, we investigated whether serum ANGPTL2 levels were associated with clinical features in breast cancer patients.
  
  
  RESULTS
  Both in vitro and in vivo experiments showed that the levels of ANGPTL2 secreted from breast cancer cells increased with cell proliferation and cancer progression. Serum ANGPTL2 levels in patients with metastatic breast cancer were significantly higher than those in healthy subjects or in patients with ductal carcinoma in situ or non-metastatic invasive ductal carcinoma. Serum ANGPTL2 levels in patients negative for estrogen receptors and progesterone receptors, particularly triple-negative cases, reflected histological grades.
  
  
  CONCLUSIONS
  These findings suggest that serum ANGPTL2 levels in breast cancer patients could represent a potential marker of breast cancer metastasis.
authors.affiliation: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto - Japan.
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Endo
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakano
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Masuda
authors.forename: Haruki
authors.initials: H
authors.lastname: Odagiri
authors.forename: Haruki
authors.initials: H
authors.lastname: Horiguchi
authors.forename: Keishi
authors.initials: K
authors.lastname: Miyata
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kadomatsu
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Motokawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Iwase
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oike
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000097:blood*; D000818:Animals; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000097:blood* / Q000473:pathology*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D018450:Disease Progression; D005260:Female; D064593:Heterografts; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009362:Neoplasm Metastasis; D064726:Triple Negative Breast Neoplasms / Q000097:blood* / Q000473:pathology*; D055815:Young Adult
chemical_list: C485792:ANGPTL2 protein, human; D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins