title: Absence of the basement membrane component nidogen 2, but not of nidogen 1, results in increased lung metastasis in mice.
abstract: Nidogen 1 and 2 are ubiquitous basement membrane (BM) components. They show a divergent expression pattern in certain adult tissues with a prominent localization of nidogen 2 in blood vessel BMs. Deletion of either nidogen 1 or 2 in mice had no effect on BM formation, suggesting complementary functions. However, studies in these mice revealed isoform-specific functions with nidogen 1-deficient mice showing neurological abnormalities and wound-healing defects not seen in the absence of nidogen 2. To investigate this further nidogen 1- or 2-deficient mice were intravenously injected with B16 murine melanoma cells, and lung metastasis was analyzed. The authors could show that loss of nidogen 2, but not of nidogen 1, significantly promotes lung metastasis of melanoma cells. Histological and ultrastructural analysis of nidogen 1- and 2-deficient lungs did not reveal differences in morphology and ultrastructure of BMs, including vessel BMs. Furthermore, deposition and distribution of the major BM components were indistinguishable between the two mouse strains. Taken together, these results suggest that absence of nidogen 2 might result in subtle changes of endothelial BMs in the lung, which would allow faster passage of tumor cells through these BMs, leading to a higher metastasis rate and more larger tumors.
authors.affiliation: Department of Dermatology, University Hospital Cologne, Cologne, Germany.
authors.forename: Sharada
authors.initials: S
authors.lastname: Mokkapati
authors.forename: Manuela
authors.initials: M
authors.lastname: Bechtel
authors.forename: Marion
authors.initials: M
authors.lastname: Reibetanz
authors.forename: Nicolai
authors.initials: N
authors.lastname: Miosge
authors.forename: Roswitha
authors.initials: R
authors.lastname: Nischt
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D045744:Cell Line, Tumor; D019084:Fluorescent Antibody Technique, Indirect; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary* / Q000648:ultrastructure; D008546:Melanoma, Experimental / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008854:Microscopy, Electron
chemical_list: D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; C112846:Nid2 protein, mouse; C029967:nidogen