title: Origins of the tumor microenvironment: quantitative assessment of adipose-derived and bone marrow-derived stroma.
abstract: To meet the requirements for rapid tumor growth, a complex array of non-neoplastic cells are recruited to the tumor microenvironment. These cells facilitate tumor development by providing matrices, cytokines, growth factors, as well as vascular networks for nutrient and waste exchange, however their precise origins remain unclear. Through multicolored tissue transplant procedures; we have quantitatively determined the contribution of bone marrow-derived and adipose-derived cells to stromal populations within syngeneic ovarian and breast murine tumors. Our results indicate that subpopulations of tumor-associated fibroblasts (TAFs) are recruited from two distinct sources. The majority of fibroblast specific protein (FSP) positive and fibroblast activation protein (FAP) positive TAFs originate from mesenchymal stem/stromal cells (MSC) located in bone marrow sources, whereas most vascular and fibrovascular stroma (pericytes, α-SMA(+) myofibroblasts, and endothelial cells) originates from neighboring adipose tissue. These results highlight the capacity for tumors to utilize multiple sources of structural cells in a systematic and discriminative manner.
authors.affiliation: Section of Molecular Hematology and Therapy, Department of Leukemia, M. D. Anderson Cancer Center, The University of Texas, Houston, Texas, United States of America.
authors.forename: Shannon
authors.initials: S
authors.lastname: Kidd
authors.forename: Erika
authors.initials: E
authors.lastname: Spaeth
authors.forename: Keri
authors.initials: K
authors.lastname: Watson
authors.forename: Jared
authors.initials: J
authors.lastname: Burks
authors.forename: Hongbo
authors.initials: H
authors.lastname: Lu
authors.forename: Ann
authors.initials: A
authors.lastname: Klopp
authors.forename: Michael
authors.initials: M
authors.lastname: Andreeff
authors.forename: Frank C
authors.initials: FC
authors.lastname: Marini
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D059016:Tumor Microenvironment
chemical_list: D015415:Biomarkers; D049452:Green Fluorescent Proteins