title: Spontaneous lung and lymph node metastasis in transgenic breast cancer is independent of the urokinase receptor uPAR.
abstract: Urokinase-type plasminogen activator (uPA) is an extracellular protease that plays a pivotal role in tumor progression. uPA activity is spatially restricted by its anchorage to high-affinity uPA receptors (uPAR) at the cell surface. High tumor tissue expression of uPA and uPAR is associated with poor prognosis in lung, breast, and colon cancer patients in clinical studies. Genetic deficiency of uPA leads to a significant reduction in metastases in the murine transgenic MMTV-PyMT breast cancer model, demonstrating a causal role for uPA in cancer dissemination. To investigate the role of uPAR in cancer progression, we analyze the effect of uPAR deficiency in the same cancer model. uPAR is predominantly expressed in stromal cells in the mouse primary tumors, similar to human breast cancer. In a cohort of MMTV-PyMT mice [uPAR-deficient (n = 31) or wild type controls (n = 33)], tumorigenesis, tumor growth, and tumor histopathology were not significantly affected by uPAR deficiency. Lung and lymph node metastases were also not significantly affected by uPAR deficiency, in contrast to the significant reduction seen in uPA-deficient mice. Taken together, our data show that the genetic absence of uPAR does not influence the outcome of the MMTV-PyMT cancer model.
authors.affiliation: The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark, kahl@novonordisk.com.
authors.forename: Kasper
authors.initials: K
authors.lastname: Almholt
authors.forename: Ole Didrik
authors.initials: OD
authors.lastname: Lærum
authors.forename: Boye Schnack
authors.initials: BS
authors.lastname: Nielsen
authors.forename: Ida Katrine
authors.initials: IK
authors.lastname: Lund
authors.forename: Leif Røge
authors.initials: LR
authors.lastname: Lund
authors.forename: John
authors.initials: J
authors.lastname: Rømer
authors.forename: Annika
authors.initials: A
authors.lastname: Jögi
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D051379:Mice; D008822:Mice, Transgenic; D055293:Receptors, Urokinase Plasminogen Activator / Q000037:antagonists & inhibitors / Q000502:physiology*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*
chemical_list: D055293:Receptors, Urokinase Plasminogen Activator