title: Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment.
abstract: The interactions of transformed cells with the surrounding stromal cells are of importance for tumor progression and metastasis. The relevance of adipocyte-derived factors to breast cancer cell survival and growth is well established. However, it remains unknown which specific adipocyte-derived factors are most critical in this process. Collagen VI is abundantly expressed in adipocytes. Collagen(-/-) mice in the background of the mouse mammary tumor virus/polyoma virus middle T oncogene (MMTV-PyMT) mammary cancer model demonstrate dramatically reduced rates of early hyperplasia and primary tumor growth. Collagen VI promotes its growth-stimulatory and pro-survival effects in part by signaling through the NG2/chondroitin sulfate proteoglycan receptor expressed on the surface of malignant ductal epithelial cells to sequentially activate Akt and beta-catenin and stabilize cyclin D1. Levels of the carboxyterminal domain of collagen VIalpha3, a proteolytic product of the full-length molecule, are dramatically upregulated in murine and human breast cancer lesions. The same fragment exerts potent growth-stimulatory effects on MCF-7 cells in vitro. Therefore, adipocytes play a vital role in defining the ECM environment for normal and tumor-derived ductal epithelial cells and contribute significantly to tumor growth at early stages through secretion and processing of collagen VI.
authors.affiliation: Department of Cell Biology, Albert Einstein Cancer Center, Albert Einstein College of Medicine, New York, New York 10461, USA.
authors.forename: Puneeth
authors.initials: P
authors.lastname: Iyengar
authors.forename: Virginia
authors.initials: V
authors.lastname: Espina
authors.forename: Terence W
authors.initials: TW
authors.lastname: Williams
authors.forename: Ying
authors.initials: Y
authors.lastname: Lin
authors.forename: David
authors.initials: D
authors.lastname: Berry
authors.forename: Linda A
authors.initials: LA
authors.lastname: Jelicks
authors.forename: Hyangkyu
authors.initials: H
authors.lastname: Lee
authors.forename: Karla
authors.initials: K
authors.lastname: Temple
authors.forename: Reed
authors.initials: R
authors.lastname: Graves
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Pollard
authors.forename: Neeru
authors.initials: N
authors.lastname: Chopra
authors.forename: Robert G
authors.initials: RG
authors.lastname: Russell
authors.forename: Ram
authors.initials: R
authors.lastname: Sasisekharan
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Trock
authors.forename: Marc
authors.initials: M
authors.lastname: Lippman
authors.forename: Valerie S
authors.initials: VS
authors.lastname: Calvert
authors.forename: Emanuel F
authors.initials: EF
authors.lastname: Petricoin
authors.forename: Lance
authors.initials: L
authors.lastname: Liotta
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Dadachova
authors.forename: Richard G
authors.initials: RG
authors.lastname: Pestell
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: Paolo
authors.initials: P
authors.lastname: Bonaldo
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D024142:Collagen Type VI / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D011120:Polyomavirus / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin
chemical_list: C495267:CTNNB1 protein, mouse; D024142:Collagen Type VI; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1