title: Host plasminogen activator inhibitor-1 promotes human skin carcinoma progression in a stage-dependent manner.
abstract: Angiogenesis and tumor expansion are associated with extracellular matrix remodeling and involve various proteases such as the plasminogen (Plg)/plasminogen activator (PA) system. Recently, several experimental data have implicated the plasminogen activator inhibitor-1 (PAI-1) in tumor angiogenesis in murine systems. However, little is known about PAI-1 functions in human skin carcinoma progression. By generating immunodeficient mice (in Rag-1-/- or nude background) deleted for PAI-1 gene (PAI-1-/-), we have evaluated the impact of host PAI-1 deficiency on the tumorigenicity of two malignant human skin keratinocyte cell lines HaCaT II-4 and HaCaT A5-RT3 forming low-grade and high-grade carcinomas, respectively. When using the surface transplantation model, angiogenesis and tumor invasion of these two cell lines are strongly reduced in PAI-1-deficient mice as compared to the wild-type control animals. After subcutaneous injection in PAI-1-/- mice, the tumor incidence is reduced for HaCaT II-4 cells, but not for those formed by HaCaT A5-RT3 cells. These data indicate that PAI-1 produced by host cells is an important contributor to earlier stages of human skin carcinoma progression. It exerts its tumor-promoting effect in a tumor stage-dependent manner, but PAI-1 deficiency is not sufficient to prevent neoplastic growth of aggressive tumors of the human skin.
authors.affiliation: Laboratory of Tumor and Development Biology, CRCE, CBIG, University of Liège, Tour de Pathologie (B23), Sart Tilman, Liège B-4000, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Maillard
authors.forename: Maud
authors.initials: M
authors.lastname: Jost
authors.forename: Maria Unni
authors.initials: MU
authors.lastname: Rømer
authors.forename: Nils
authors.initials: N
authors.lastname: Brunner
authors.forename: Xavier
authors.initials: X
authors.lastname: Houard
authors.forename: Annabelle
authors.initials: A
authors.lastname: Lejeune
authors.forename: Carine
authors.initials: C
authors.lastname: Munaut
authors.forename: Khalid
authors.initials: K
authors.lastname: Bajou
authors.forename: Laurence
authors.initials: L
authors.lastname: Melen
authors.forename: Keld
authors.initials: K
authors.lastname: Dano
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Norbert E
authors.initials: NE
authors.lastname: Fusenig
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Foidart
authors.forename: Agnès
authors.initials: A
authors.lastname: Noel
mesh_terms: D000818:Animals; D018450:Disease Progression; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000502:physiology*; D012878:Skin Neoplasms / Q000098:blood supply / Q000209:etiology / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000637:transplantation
chemical_list: D018398:Homeodomain Proteins; D017395:Plasminogen Activator Inhibitor 1; C064658:RAG-1 protein
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