Host plasminogen activator inhibitor-1 promotes human skin carcinoma progression in a stage-dependent manner

[en] 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.

Disciplines :

Oncology

Author, co-author :

Maillard, Catherine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement

Jost, M.

Romer, M. U.

Brunner, N.

Houard, X.

Lejeune, Annabelle ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire

Munaut, Carine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement

Bajou, Khalid ; Université de Liège - ULiège > Département des sciences de la vie > Biologie et génétique moléculaire

Melen-Lamalle, Laurence ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement

Dano, K.

More authors (4 more)

Language :

English

Title :

Host plasminogen activator inhibitor-1 promotes human skin carcinoma progression in a stage-dependent manner

Publication date :

January 2005

Journal title :

Neoplasia

ISSN :

1522-8002

eISSN :

1476-5586

Publisher :

BC Decker, Hamilton Ont, Canada

Volume :

Issue :

Pages :

57-66

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 25 March 2009

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