Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment

Puneeth Iyengar, Virginia Espina, Terence W Williams, Ying Lin, David Berry, Linda A Jelicks, Hyangkyu Lee, Karla Temple, Reed Graves, Jeffrey Pollard, Neeru Chopra, Robert G Russell, Ram Sasisekharan, Bruce J Trock, Marc Lippman, Valerie S Calvert, Emanuel F Petricoin, Lance Liotta, Ekaterina Dadachova, Richard G PestellMichael P Lisanti, Paolo Bonaldo, Philipp E Scherer

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)1163-76
Number of pages14
JournalJournal of Clinical Investigation
Issue number5
Publication statusPublished - May 2005

Keywords / Materials (for Non-textual outputs)

  • Adipocytes
  • Animals
  • Collagen Type VI
  • Cyclin D1
  • Cytoskeletal Proteins
  • Female
  • Immunohistochemistry
  • Mammary Neoplasms, Animal
  • Mice
  • Polyomavirus
  • Trans-Activators
  • beta Catenin


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