This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Ossowski, L. Search for Related Content PubMed PubMed Citation Articles by Ossowski, L.

Invasion of Connective Tissue by Human Carcinoma Cell Lines: Requirement for Urokinase, Urokinase Receptor, and Interstitial Collagenase¹

Division of Medical Oncology, The Mount Sinai School of Medicine, New York, New York 10029

We have screened six human squamous carcinoma cell lines for their ability to invade connective tissue by using the experimentally modified chorioallantoic membrane of a chick embryo as an in vivo model of invasion. In confirmation of our earlier studies, all the invasive cell lines expressed high levels of surface-bound urokinase type plasminogen activator (uPA). However, some cell lines expressing this activity were not invasive, suggesting that surface uPA, although necessary, was not sufficient. Since in addition to fibronectin, that can be degraded by uPA or plasmin, chorioallantoic membrane connective tissue contains collagen, we examined the profile of collagenases secreted by the various cell lines in search for an activity that would coincide with the invasive phenotype. We found, using gelatin substrate gels, that type IV gelatinase was produced by all six cell types tested, three cell types produced the M_r 92,000 gelatinase, and three a lower-molecular-weight activity, which we identified by immunoprecipitation with specific antibodies, and by a direct assay of activity, as interstitial collagenase. Only the latter cells were found to be highly invasive.

We showed previously that continuous culture in vitro of one of the carcinoma cell lines, HEp3, led to a gradual extinction of their malignant phenotype. To confirm the correlation between invasion and the production of interstitial collagenase, we examined these two functions in cells freshly isolated from a HEp3 tumor and intermittently during passage in vitro. We found that, although the surface uPA activity was slightly diminished in the in vitro grown cultures, it was still within the range of values found in highly malignant cells, suggesting that it is not the reason for the decrease in invasiveness. In contrast, the reduction in interstitial collagenase closely followed the loss of the invasive phenotype; after 30 in vitro passages the cells were almost completely devoid of interstitial collagenase and unable to invade. The decrease in collagenase activity was not the result of an increased tissue inhibitor of metalloproteinases production.

¹ This work was supported by USPHS Research Grant CA-40758 and the Samuel Waxman Cancer Research Foundation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 2/20/92. Accepted 10/ 2/92.

This article has been cited by other articles:

				L.-Y. Luo, S. J.C. Shan, M. B. Elliott, A. Soosaipillai, and E. P. Diamandis Purification and Characterization of Human Kallikrein 11, a Candidate Prostate and Ovarian Cancer Biomarker, from Seminal Plasma Clin. Cancer Res., February 1, 2006; 12(3): 742 - 750. [Abstract] [Full Text] [PDF]

				A. Zijlstra, R. Mellor, G. Panzarella, R. T. Aimes, J. D. Hooper, N. D. Marchenko, and J. P. Quigley A Quantitative Analysis of Rate-limiting Steps in the Metastatic Cascade Using Human-specific Real-Time Polymerase Chain Reaction Cancer Res., December 1, 2002; 62(23): 7083 - 7092. [Abstract] [Full Text] [PDF]

				T.-a. Masuda, H. Inoue, H. Sonoda, S. Mine, Y. Yoshikawa, K. Nakayama, K.-I. Nakayama, and M. Mori Clinical and Biological Significance of S-Phase Kinase-associated Protein 2 (Skp2) Gene Expression in Gastric Carcinoma: Modulation of Malignant Phenotype by Skp2 Overexpression, Possibly via p27 Proteolysis Cancer Res., July 1, 2002; 62(13): 3819 - 3825. [Abstract] [Full Text] [PDF]

				S. Yano, H. Shinohara, R. S. Herbst, H. Kuniyasu, C. D. Bucana, L. M. Ellis, and I. J. Fidler Production of Experimental Malignant Pleural Effusions Is Dependent on Invasion of the Pleura and Expression of Vascular Endothelial Growth Factor/Vascular Permeability Factor by Human Lung Cancer Cells Am. J. Pathol., December 1, 2000; 157(6): 1893 - 1903. [Abstract] [Full Text] [PDF]

				B. Schroeder, M. D. P. Boyle, B. R. Sheerin, A. C. Asbury, and R. Lottenberg Species Specificity of Plasminogen Activation and Acquisition of Surface-Associated Proteolytic Activity by Group C Streptococci Grown in Plasma Infect. Immun., December 1, 1999; 67(12): 6487 - 6495. [Abstract] [Full Text] [PDF]

				J. A. A. Ghiso, K. Kovalski, and L. Ossowski Tumor Dormancy Induced by Downregulation of Urokinase Receptor in Human Carcinoma Involves Integrin and MAPK Signaling J. Cell Biol., October 4, 1999; 147(1): 89 - 104. [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]

				E. Allaire, D. Hasenstab, R. D. Kenagy, B. Starcher, M. M. Clowes, and A. W. Clowes Prevention of Aneurysm Development and Rupture by Local Overexpression of Plasminogen Activator Inhibitor-1 Circulation, July 21, 1998; 98(3): 249 - 255. [Abstract] [Full Text] [PDF]

				R.D. Kenagy, S. Vergel, E. Mattsson, M. Bendeck, M.A. Reidy, and A.W. Clowes The Role of Plasminogen, Plasminogen Activators, and Matrix Metalloproteinases in Primate Arterial Smooth Muscle Cell Migration Arterioscler Thromb Vasc Biol, November 1, 1996; 16(11): 1373 - 1382. [Abstract] [Full Text]

				N. Zempo, N. Koyama, R. D. Kenagy, H. J. Lea, and A. W. Clowes Regulation of Vascular Smooth Muscle Cell Migration and Proliferation In Vitro and in Injured Rat Arteries by a Synthetic Matrix Metalloproteinase Inhibitor Arterioscler Thromb Vasc Biol, January 1, 1996; 16(1): 28 - 33. [Abstract] [Full Text]

				A. Y. Strongin, I. Collier, G. Bannikov, B. L. Marmer, G. A. Grant, and G. I. Goldberg Mechanism Of Cell Surface Activation Of 72-kDa Type IV Collagenase J. Biol. Chem., March 10, 1995; 270(10): 5331 - 5338. [Abstract] [Full Text] [PDF]