title: Complementary populations of human adipose CD34+ progenitor cells promote growth, angiogenesis, and metastasis of breast cancer.
abstract: Obesity is associated with an increased frequency, morbidity, and mortality of several types of neoplastic diseases, including postmenopausal breast cancer. We found that human adipose tissue contains two populations of progenitors with cooperative roles in breast cancer. CD45(-)CD34(+)CD31(+)CD13(-)CCRL2(+) endothelial cells can generate mature endothelial cells and capillaries. Their cancer-promoting effect in the breast was limited in the absence of CD45(-)CD34(+)CD31(-)CD13(+)CD140b(+) mesenchymal progenitors/adipose stromal cells (ASC), which generated pericytes and were more efficient than endothelial cells in promoting local tumor growth. Both endothelial cells and ASCs induced epithelial-to-mesenchymal transition (EMT) gene expression in luminal breast cancer cells. Endothelial cells (but not ASCs) migrated to lymph nodes and to contralateral nascent breast cancer lesions where they generated new vessels. In vitro and in vivo, endothelial cells were more efficient than ASCs in promoting tumor migration and in inducing metastases. Granulocyte colony-stimulating factor (G-CSF) effectively mobilized endothelial cells (but not ASCs), and the addition of chemotherapy and/or of CXCR4 inhibitors did not increase endothelial cell or ASC blood mobilization. Our findings suggest that adipose tissue progenitor cells cooperate in driving progression and metastatic spread of breast cancer.
authors.affiliation: Authors' Affiliations: Laboratory of Hematology-Oncology, Department of Pathology, and Division of Plastic Surgery, European Institute of Oncology; and Division of Pathology, San Paolo University Hospital, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Orecchioni
authors.forename: Giuliana
authors.initials: G
authors.lastname: Gregato
authors.forename: Ines
authors.initials: I
authors.lastname: Martin-Padura
authors.forename: Francesca
authors.initials: F
authors.lastname: Reggiani
authors.forename: Paola
authors.initials: P
authors.lastname: Braidotti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mancuso
authors.forename: Angelica
authors.initials: A
authors.lastname: Calleri
authors.forename: Jessica
authors.initials: J
authors.lastname: Quarna
authors.forename: Paola
authors.initials: P
authors.lastname: Marighetti
authors.forename: Chiara
authors.initials: C
authors.lastname: Aldeni
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Pruneri
authors.forename: Stefano
authors.initials: S
authors.lastname: Martella
authors.forename: Andrea
authors.initials: A
authors.lastname: Manconi
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Petit
authors.forename: Mario
authors.initials: M
authors.lastname: Rietjens
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertolini
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology*; D052436:Adipose Tissue, White / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000556:secondary*; D008207:Lymphatic Metastasis; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D018952:Antigens, CD34; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor