title: CD13-positive bone marrow-derived myeloid cells promote angiogenesis, tumor growth, and metastasis.
abstract: Angiogenesis is fundamental to tumorigenesis and an attractive target for therapeutic intervention against cancer. We have recently demonstrated that CD13 (aminopeptidase N) expressed by nonmalignant host cells of unspecified types regulate tumor blood vessel development. Here, we compare CD13 wild-type and null bone marrow-transplanted tumor-bearing mice to show that host CD13(+) bone marrow-derived cells promote cancer progression via their effect on angiogenesis. Furthermore, we have identified CD11b(+)CD13(+) myeloid cells as the immune subpopulation directly regulating tumor blood vessel development. Finally, we show that these cells are specifically localized within the tumor microenvironment and produce proangiogenic soluble factors. Thus, CD11b(+)CD13(+) myeloid cells constitute a population of bone marrow-derived cells that promote tumor progression and metastasis and are potential candidates for the development of targeted antiangiogenic drugs.
authors.affiliation: David H. Koch Center, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Dondossola
authors.forename: Roberto
authors.initials: R
authors.lastname: Rangel
authors.forename: Liliana
authors.initials: L
authors.lastname: Guzman-Rojas
authors.forename: Elena M
authors.initials: EM
authors.lastname: Barbu
authors.forename: Hitomi
authors.initials: H
authors.lastname: Hosoya
authors.forename: Lisa S
authors.initials: LS
authors.lastname: St John
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Molldrem
authors.forename: Angelo
authors.initials: A
authors.lastname: Corti
authors.forename: Richard L
authors.initials: RL
authors.lastname: Sidman
authors.forename: Wadih
authors.initials: W
authors.lastname: Arap
authors.forename: Renata
authors.initials: R
authors.lastname: Pasqualini
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D039481:CD11b Antigen; D018826:CD13 Antigens; D045744:Cell Line, Tumor; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology
chemical_list: D043925:Angiogenesis Inducing Agents; D039481:CD11b Antigen; D018826:CD13 Antigens
keywords: mouse models; protease; stromal cells; vascular pericytes