This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bruckner, A. Articles by Remold, H. G. Search for Related Content PubMed PubMed Citation Articles by Bruckner, A. Articles by Remold, H. G.

Endogenous Receptor-bound Urokinase Mediates Tissue Invasion of the Human Lung Carcinoma Cell Lines A549 and Calu-1¹

Department of Rheumatology and Immunology, Brigham and Women's Hospital [A. B., H. G. R.], Department of Pulmonary Medicine, New England Deaconess Hospital [A. E. F.], and Harvard Medical School [A. B., A. E. F., H. G. R.], Boston, Massachusetts 02115; and Departments of Orthopedics and Physiology, University of Vienna, Vienna, Austria [J. C. K., B. R. B.]

Macrophage colony-stimulating factor (CSF-1) increases the tissue invasive potential of the CSF-1 receptor-bearing lung carcinoma cell lines A549 and Calu-1 by increasing the number of endogenously bound urokinase-type plasminogen activators (u-PA)s on these cells. CSF-1, at concentrations which optimize invasion of A549 and Calu-1 cells into human amnion membranes (250 ng/ml), maximally augments the number of u-PA receptors occupied by endogenously produced urokinase. Preincubation of A549 and Calu-1 cells with the anti-u-PA monoclonal antibody MPW5UK (25 µg/ml) or with a 20- to 40-fold stoichiometric excess of fluid phase type 2 plasminogen activator inhibitor abrogates invasiveness, indicating that functionally active cell surface u-PA is essential for tissue invasion. In contrast, fluid phase type 1 plasminogen activator inhibitor (PAI-1, 5–15 units/ml) does not inhibit invasiveness unless preincubated with the amnion membranes. Inhibition of invasion by PAI-1 is abolished by presaturating the amnion membranes with anti-itronectin monoclonal antibody (10 µg/ml) which prevents binding of PAI-1 to tissue-associated vitronectin. Binding of PAI-1 to tissue vitronectin is therefore a prerequisite for its inhibitory action. Thus, endogenously receptor-bound u-PA is the primary protease mediating CSF-1-induced tissue invasiveness of the lung carcinoma cell lines A549 and Calu-1.

¹ Supported by National Institutes of Health Research Grant AI22532 and by a grant from the Oncology Foundation, University of Vienna, Austria.

² To whom requests for reprints should be addressed, at Department of Rheumatology/Immunology, Brigham and Women's Hospital, Room 513, LMRC, 221 Longwood Ave., Boston, MA 02115.

Received 11/ 1/91. Accepted 3/25/92.

This article has been cited by other articles:

				S. Aharinejad, D. Abraham, P. Paulus, H. Abri, M. Hofmann, K. Grossschmidt, R. Schafer, E. R. Stanley, and R. Hofbauer Colony-stimulating Factor-1 Antisense Treatment Suppresses Growth of Human Tumor Xenografts in Mice Cancer Res., September 15, 2002; 62(18): 5317 - 5324. [Abstract] [Full Text] [PDF]

				H. Shiomi, Y. Eguchi, T. Tani, M. Kodama, and T. Hattori Cellular Distribution and Clinical Value of Urokinase-Type Plasminogen Activator, Its Receptor, and Plasminogen Activator Inhibitor-2 in Esophageal Squamous Cell Carcinoma Am. J. Pathol., February 1, 2000; 156(2): 567 - 575. [Abstract] [Full Text] [PDF]

				H. Allgayer, H. Wang, Y. Wang, M. M. Heiss, R. Bauer, O. Nyormoi, and D. Boyd Transactivation of the Urokinase-type Plasminogen Activator Receptor Gene through a Novel Promoter Motif Bound with an Activator Protein-2alpha -related Factor J. Biol. Chem., February 19, 1999; 274(8): 4702 - 4714. [Abstract] [Full Text] [PDF]

				N. Keshava, S. Gubba, and R. R. Tekmal Overexpression of Macrophage Colony-Stimulating Factor (CSF-I) and Its Receptor, c-fms, in Normal Ovarian Granulosa Cells Leads to Cell Proliferation and Tumorigenesis Reproductive Sciences, January 1, 1999; 6(1): 41 - 49. [Abstract] [PDF]

				Y. Koshelnick, M. Ehart, P. Hufnagl, P. C. Heinrich, and B. R. Binder Urokinase Receptor Is Associated with the Components of the JAK1/STAT1 Signaling Pathway and Leads to Activation of This Pathway upon Receptor Clustering in the Human Kidney Epithelial Tumor Cell Line TCL-598 J. Biol. Chem., November 7, 1997; 272(45): 28563 - 28567. [Abstract] [Full Text] [PDF]