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 Nakajima, M. Articles by Nicolson, G. L. Search for Related Content PubMed PubMed Citation Articles by Nakajima, M. Articles by Nicolson, G. L.

Degradation of Basement Membrane Type IV Collagen and Lung Subendothelial Matrix by Rat Mammary Adenocarcinoma Cell Clones of Differing Metastatic Potentials¹

Department of Tumor Biology, The University of Texas M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77030

A series of rat 13762NF mammary adenocarcinoma cell clones and subclones of various lung metastatic potentials were examined for their abilities to degrade rat lung subendothelial matrix and purified basement membrane type IV collagen. Metastatic potentials were simultaneously determined based on the ability to form "spontaneous" lung metastases after s.c. injection or "experimental" lung metastases after i.v. injection of cells. Microvessel endothelial cells isolated from rat lung were grown in vitro, and the subendothelial matrix containing type IV collagen was metabolically labeled with [³H]proline. When mammary adenocarcinoma cells were placed on the isolated subendothelial matrix, fragmentation and solubilization of [³H]proline-labeled components were observed; highly metastatic 13762NF cells solubilized the matrix at higher rates than did poorly metastatic cells. The 13762NF cells were assayed for type IV collagenolytic activity using [³H]proline-labeled type IV collagen purified from Engelbreth-Holm-Swarm tumor as a substrate. We found excellent correlation between the type IV collagenolytic activities of living cells and their "spontaneous" lung metastatic potentials (r = 0.993). The levels of type IV collagenolytic activity in the conditioned medium depended on the cell culture conditions. In the presence or absence of acidtreated fetal bovine serum, highly metastatic cells secreted higher amounts of type IV collagenolytic enzymes in active and latent forms than did poorly metastatic cells. Incubation of procollagen type IV with medium conditioned by highly metastatic 13762NF cells and treated with trypsin resulted in the production of several large fragments characteristic of type IV collagen. The results suggest that enzymatic degradation of basement membrane type IV collagen is important in lung metastasis of 13762NF mammary adenocarcinoma cells.

¹ Supported by USPHS National Cancer Institute Grant RO1-CA28844 and R35-CA44352 (O.I.A.) to G. L. N. and RO1-CA41524 to M. N.

² Present address: Cancer Research, The Upjohn Company, Kalamazoo, MI 49001.

³ To whom requests for reprints should be addressed, at the Department of Tumor Biology, The University of Texas M. D. Anderson Hospital and Tumor Institute, Houston, TX 77030.

Received 3/24/86. Revised 6/16/87. Accepted 6/23/87.

This article has been cited by other articles:

				J.-i. Hamada, D. Nakata, D. Nakae, Y. Kobayashi, H. Akai, Y. Konishi, F. Okada, T. Shibata, M. Hosokawa, and T. Moriuchi Increased Oxidative DNA Damage in Mammary Tumor Cells by Continuous Epidermal Growth Factor Stimulation J Natl Cancer Inst, February 7, 2001; 93(3): 214 - 219. [Abstract] [Full Text] [PDF]

				J. B. Wyckoff, J. E. Segall, and J. S. Condeelis The Collection of the Motile Population of Cells from a Living Tumor Cancer Res., October 1, 2000; 60(19): 5401 - 5404. [Abstract] [Full Text]

				M. Määttä, Y. Soini, A. Liakka, and H. Autio-Harmainen Differential Expression of Matrix Metalloproteinase (MMP)-2, MMP-9, and Membrane Type 1-MMP in Hepatocellular and Pancreatic Adenocarcinoma: Implications for Tumor Progression and Clinical Prognosis Clin. Cancer Res., July 1, 2000; 6(7): 2726 - 2734. [Abstract] [Full Text]

				M. Hanzawa, M. Shindoh, F. Higashino, M. Yasuda, N. Inoue, K. Hida, M. Ono, T. Kohgo, M. Nakamura, K.-i. Notani, et al. Hepatocyte growth factor upregulates E1AF that induces oral squamous cell carcinoma cell invasion by activating matrix metalloproteinase genes Carcinogenesis, June 1, 2000; 21(6): 1079 - 1085. [Abstract] [Full Text] [PDF]

				S. Koochekpour, M. Jeffers, P. H. Wang, C. Gong, G. A. Taylor, L. M. Roessler, R. Stearman, J. R. Vasselli, W. G. Stetler-Stevenson, W. G. Kaelin Jr., et al. The von Hippel-Lindau Tumor Suppressor Gene Inhibits Hepatocyte Growth Factor/Scatter Factor-Induced Invasion and Branching Morphogenesis in Renal Carcinoma Cells Mol. Cell. Biol., September 1, 1999; 19(9): 5902 - 5912. [Abstract] [Full Text] [PDF]

				H. Takeshita, T. Yoshizaki, W. E. Miller, H. Sato, M. Furukawa, J. S. Pagano, and N. Raab-Traub Matrix Metalloproteinase 9 Expression Is Induced by Epstein-Barr Virus Latent Membrane Protein 1 C-Terminal Activation Regions 1 and 2 J. Virol., July 1, 1999; 73(7): 5548 - 5555. [Abstract] [Full Text]

				Z.-S. Zeng, A. M. Cohen, and J. G. Guillem Loss of basement membrane type IV collagen is associated with increased expression of metalloproteinases 2 and 9 (MMP-2 and MMP-9) during human colorectal tumorigenesis Carcinogenesis, May 1, 1999; 20(5): 749 - 755. [Abstract] [Full Text] [PDF]

				T. Iizasa, T. Fujisawa, M. Suzuki, S.-i. Motohashi, K. Yasufuku, T. Yasukawa, M. Baba, and M. Shiba Elevated Levels of Circulating Plasma Matrix Metalloproteinase 9 in Non-Small Cell Lung Cancer Patients Clin. Cancer Res., January 1, 1999; 5(1): 149 - 153. [Abstract] [Full Text] [PDF]

				T. Yoshizaki, H. Sato, M. Furukawa, and J. S. Pagano The expression of matrix metalloproteinase 9 is enhanced by Epstein-Barr virus latent membrane protein 1 PNAS, March 31, 1998; 95(7): 3621 - 3626. [Abstract] [Full Text] [PDF]

				C. H. Bu and T. Pourmotabbed Mechanism of Ca2+-dependent Activity of Human Neutrophil Gelatinase B J. Biol. Chem., June 14, 1996; 271(24): 14308 - 14315. [Abstract] [Full Text] [PDF]

				H. Birkedal-Hansen, W.G.I. Moore, M.K. Bodden, L.J. Windsor, B. Birkedal-Hansen, A. DeCarlo, and J.A. Engler Matrix Metalloproteinases: A Review Critical Reviews in Oral Biology & Medicine, January 1, 1993; 4(2): 197 - 250. [Abstract] [Full Text] [PDF]

				R Khokha, P Waterhouse, S Yagel, P. Lala, C. Overall, G Norton, and D. Denhardt Antisense RNA-induced reduction in murine TIMP levels confers oncogenicity on Swiss 3T3 cells Science, February 17, 1989; 243(4893): 947 - 950. [Abstract] [PDF]

				U. T. Shankavaram, W.-C. Lai, S. Netzel-Arnett, P. R. Mangan, J. A. Ardans, N. Caterina, W. G. Stetler-Stevenson, H. Birkedal-Hansen, and L. M. Wahl Monocyte Membrane Type 1-Matrix Metalloproteinase. PROSTAGLANDIN-DEPENDENT REGULATION AND ROLE IN METALLOPROTEINASE-2 ACTIVATION J. Biol. Chem., May 25, 2001; 276(22): 19027 - 19032. [Abstract] [Full Text] [PDF]