Does plasminogen activator inhibitor-1 drive lymphangiogenesis?

• Published in: PloS one 2010-03, Vol.5 (3), p.e9653-e9653
• Main Authors: Bruyère, Françoise, Melen-Lamalle, Laurence, Blacher, Silvia, Detry, Benoît, Masset, Anne, Lecomte, Julie, Lambert, Vincent, Maillard, Catherine, Høyer-Hansen, Gunilla, Lund, Leif R, Foidart, Jean-Michel, Noël, Agnès
• Format: Article
• Language: English
• Subjects: Analysis; Angiogenesis; Animal models; Animals; Antigens, Polyomavirus Transforming - metabolism; Bacterial infections; Biochemistry, biophysics & molecular biology; Biochimie, biophysique & biologie moléculaire; Biology; Breast cancer; Cancer metastasis; Carcinoma; Cardiovascular Disorders/Valvular Disease; Cardiovascular Disorders/Vascular Biology; Cell Biology; Cell Biology/Extra-Cellular Matrix; Cell Line, Tumor; Cell survival; Cornea; Endothelial cells; Extracellular matrix; Female; Genetic engineering; Heterozygote; Humans; Inflammation; Inhibitors; Laboratory animals; Life sciences; Long terminal repeat; Lung cancer; Lymphangioma; Lymphangioma - metabolism; Lymphatic system; Male; Mammary gland; Mammary Tumor Virus, Mouse - metabolism; Metastases; Metastasis; Mice; Mice, Transgenic; Models, Biological; Morphogenesis; Neoplasm Metastasis; Oncology/Breast Cancer; Ophthalmology/Corneal Disorders; Physiological aspects; Physiology; Plasminogen Activator Inhibitor 1 - physiology; Plasminogen activator inhibitors; Polyamide-imides; Proteases; Proteolysis; Rodents; Sciences du vivant; Transgenic mice; Transplants & implants; Tumor antigens; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0009653

The purpose of this study is to explore the function of plasminogen activator inhibitor-1 (PAI-1) during pathological lymphangiogenesis. PAI-1, the main physiological inhibitor of plasminogen activators is involved in pathological angiogenesis at least by controlling extracellular proteolysis and by regulating endothelial cell survival and migration. Protease system's role in lymphangiogenesis is unknown yet. Thus, based on its important pro-angiogenic effect, we hypothesized that PAI-1 may regulate lymphangiogenesis associated at least with metastatic dissemination of cancer cells. To address this issue, we studied the impact of PAI-1 deficiency in various murine models of tumoral lymphangiogenesis. Wild-type PAI-1 proficient mice were used as controls. We provide for the first time evidence that PAI-1 is dispensable for tumoral lymphangiogenesis associated with breast cancers either induced by mammary carcinoma cell injection or spontaneously appearing in transgenic mice expressing the polyomavirus middle T antigen (PymT) under the control of a mouse mammary tumor virus long-terminal repeat promoter (MMTV-LTR). We also investigated inflammation-related lymphatic vessel recruitment by using two inflammatory models. PAI-1 deficiency did neither affect the development of lymphangioma nor burn-induced corneal lymphangiogenesis. These novel data suggest that vascular remodelling associated with lymphangiogenesis and angiogenesis involve different molecular determinants. PAI-1 does not appear as a potential therapeutic target to counteract pathological lymphangiogenesis.