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 Long, L. Articles by Brodt, P. Search for Related Content PubMed PubMed Citation Articles by Long, L. Articles by Brodt, P.

Regulation of the M_r 72,000 Type IV Collagenase by the Type I Insulin-like Growth Factor Receptor¹

Departments of Surgery [L. L., R. N., P. B.], Medicine [P. B.], and Oncology [P. B.], McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada H3A 1A1

The M_r 72,000 type IV collagenase [matrix metalloproteinase 2 (MMP-2)] is known to play a central role in the process of invasion and metastasis, but its regulation is not clearly understood. We investigated the role of the type I insulin-like growth factor (IGF-I) in the regulation of tumor cell invasion and the synthesis of MMP-2. Highly invasive murine Lewis lung carcinoma subline H-59 cells, in which expression of the IGF-I receptor (IGF-IR) was blocked by antisense mRNA, had a significantly reduced invasion in reconstituted basement membrane (Matrigel) as compared with that of controls. These cells had a decrease of up to 6-fold in the level of MMP-2 mRNA transcripts, as assessed by reverse transcription-PCR, and a corresponding reduction in protein synthesis, as assessed by the Western blot assay and gelatin zymography. Conversely, overexpression of IGF-IR in a second, poorly invasive carcinoma subline (M-27) with low endogenous levels of the receptor increased MMP-2 mRNA and protein expression by up to 7.5- and 4-fold, respectively. Ligand-mediated activation of the IGF-IR induced MMP-2 synthesis in both cell types. The results identify IGF-I as a regulator of MMP-2 expression and cellular invasion.

¹ Supported by a grant from the Medical Research Council of Canada (to P.B.).

² To whom requests for reprints should be addressed, at Surgical Research Laboratories, Royal Victoria Hospital, 687 Pine Avenue West, Room H6.25, Montreal, Quebec, Canada H3A 1A1.

Received 4/17/98. Accepted 6/16/98.

This article has been cited by other articles:

				S. Li, D. Zhang, L. Yang, J. V. Burnier, N. Wang, R. Lin, E. R. Lee, R. I. Glazer, and P. Brodt The IGF-I Receptor Can Alter the Matrix Metalloproteinase Repertoire of Tumor Cells through Transcriptional Regulation of PKC-{alpha} Mol. Endocrinol., December 1, 2009; 23(12): 2013 - 2025. [Abstract] [Full Text] [PDF]

				Y. Adachi, R. Li, H. Yamamoto, Y. Min, W. Piao, Y. Wang, A. Imsumran, H. Li, Y. Arimura, C.-T. Lee, et al. Insulin-like growth factor-I receptor blockade reduces the invasiveness of gastrointestinal cancers via blocking production of matrilysin Carcinogenesis, August 1, 2009; 30(8): 1305 - 1313. [Abstract] [Full Text] [PDF]

				A. Imsumran, Y. Adachi, H. Yamamoto, R. Li, Y. Wang, Y. Min, W. Piao, K. Nosho, Y. Arimura, Y. Shinomura, et al. Insulin-like growth factor-I receptor as a marker for prognosis and a therapeutic target in human esophageal squamous cell carcinoma Carcinogenesis, May 1, 2007; 28(5): 947 - 956. [Abstract] [Full Text] [PDF]

				A. A. Samani, S. Yakar, D. LeRoith, and P. Brodt The Role of the IGF System in Cancer Growth and Metastasis: Overview and Recent Insights Endocr. Rev., February 1, 2007; 28(1): 20 - 47. [Abstract] [Full Text] [PDF]

				C.-M. Park, M.-J. Park, H.-J. Kwak, H.-C. Lee, M.-S. Kim, S.-H. Lee, I.-C. Park, C. H. Rhee, and S.-I. Hong Ionizing Radiation Enhances Matrix Metalloproteinase-2 Secretion and Invasion of Glioma Cells through Src/Epidermal Growth Factor Receptor-Mediated p38/Akt and Phosphatidylinositol 3-Kinase/Akt Signaling Pathways. Cancer Res., September 1, 2006; 66(17): 8511 - 8519. [Abstract] [Full Text] [PDF]

				S.-H. Oh, W.-Y. Kim, J.-H. Kim, M. N. Younes, A. K. El-Naggar, J. N. Myers, M. Kies, P. Cohen, F. Khuri, W. K. Hong, et al. Identification of Insulin-Like Growth Factor Binding Protein-3 as a Farnesyl Transferase Inhibitor SCH66336-Induced Negative Regulator of Angiogenesis in Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., January 15, 2006; 12(2): 653 - 661. [Abstract] [Full Text] [PDF]

				L. Lynch, P. I. Vodyanik, D. Boettiger, and M. A. Guvakova Insulin-like Growth Factor I Controls Adhesion Strength Mediated by {alpha}5{beta}1 Integrins in Motile Carcinoma Cells Mol. Biol. Cell, January 1, 2005; 16(1): 51 - 63. [Abstract] [Full Text] [PDF]

				D. Zhang, M. Bar-Eli, S. Meloche, and P. Brodt Dual Regulation of MMP-2 Expression by the Type 1 Insulin-like Growth Factor Receptor: THE PHOSPHATIDYLINOSITOL 3-KINASE/Akt AND Raf/ERK PATHWAYS TRANSMIT OPPOSING SIGNALS J. Biol. Chem., May 7, 2004; 279(19): 19683 - 19690. [Abstract] [Full Text] [PDF]

				M. Sekharam, H. Zhao, M. Sun, Q. Fang, Q. Zhang, Z. Yuan, H. C. Dan, D. Boulware, J. Q. Cheng, and D. Coppola Insulin-like Growth Factor 1 Receptor Enhances Invasion and Induces Resistance to Apoptosis of Colon Cancer Cells through the Akt/Bcl-xL Pathway Cancer Res., November 15, 2003; 63(22): 7708 - 7716. [Abstract] [Full Text] [PDF]

				M. Yasumaru, S. Tsuji, M. Tsujii, T. Irie, M. Komori, A. Kimura, T. Nishida, Y. Kakiuchi, N. Kawai, H. Murata, et al. Inhibition of Angiotensin II Activity Enhanced the Antitumor Effect of Cyclooxygenase-2 Inhibitors via Insulin-Like Growth Factor I Receptor Pathway Cancer Res., October 15, 2003; 63(20): 6726 - 6734. [Abstract] [Full Text] [PDF]

				H. E. Turner, A. L. Harris, S. Melmed, and J. A. H. Wass Angiogenesis in Endocrine Tumors Endocr. Rev., October 1, 2003; 24(5): 600 - 632. [Abstract] [Full Text] [PDF]

				H. Wang, H. Wang, W. Shen, H. Huang, L. Hu, L. Ramdas, Y.-H. Zhou, W. S-L. Liao, G. N. Fuller, and W. Zhang Insulin-like Growth Factor Binding Protein 2 Enhances Glioblastoma Invasion by Activating Invasion-enhancing Genes Cancer Res., August 1, 2003; 63(15): 4315 - 4321. [Abstract] [Full Text] [PDF]

				Y. Tang, D. Zhang, L. Fallavollita, and P. Brodt Vascular Endothelial Growth Factor C Expression and Lymph Node Metastasis Are Regulated by the Type I Insulin-like Growth Factor Receptor Cancer Res., March 15, 2003; 63(6): 1166 - 1171. [Abstract] [Full Text] [PDF]

				M. E. Stearns, M. Wang, Y. Hu, F. U. Garcia, and J. Rhim Interleukin 10 Blocks Matrix Metalloproteinase-2 and Membrane Type 1-Matrix Metalloproteinase Synthesis in Primary Human Prostate Tumor Lines Clin. Cancer Res., March 1, 2003; 9(3): 1191 - 1199. [Abstract] [Full Text] [PDF]

				A. Solomon, M. Grueterich, D.-Q. Li, D. Meller, S.-B. Lee, and S. C. G. Tseng Overexpression of Insulin-like Growth Factor-Binding Protein-2 in Pterygium Body Fibroblasts Invest. Ophthalmol. Vis. Sci., February 1, 2003; 44(2): 573 - 580. [Abstract] [Full Text] [PDF]

				S. Tanno, S. Tanno, Y. Mitsuuchi, D. A. Altomare, G.-H. Xiao, and J. R. Testa AKT Activation Up-Regulates Insulin-like Growth Factor I Receptor Expression and Promotes Invasiveness of Human Pancreatic Cancer Cells Cancer Res., January 1, 2001; 61(2): 589 - 593. [Abstract] [Full Text]

				J. Araya, M. Maruyama, K. Sassa, T. Fujita, R. Hayashi, S. Matsui, T. Kashii, N. Yamashita, E. Sugiyama, and M. Kobayashi Ionizing radiation enhances matrix metalloproteinase-2 production in human lung epithelial cells Am J Physiol Lung Cell Mol Physiol, January 1, 2001; 280(1): L30 - L38. [Abstract] [Full Text] [PDF]

				K. Asosingh, U. Gunthert, M. H. C. Bakkus, H. De Raeve, E. Goes, I. Van Riet, B. Van Camp, and K. Vanderkerken In Vivo Induction of Insulin-like Growth Factor-I Receptor and CD44v6 Confers Homing and Adhesion to Murine Multiple Myeloma Cells Cancer Res., June 1, 2000; 60(11): 3096 - 3104. [Abstract] [Full Text] [PDF]

				A. Janowska-Wieczorek, L. A. Marquez, J.-M. Nabholtz, M. L. Cabuhat, J. Montano, H. Chang, J. Rozmus, J. A. Russell, D. R. Edwards, and A. R. Turner Growth Factors and Cytokines Upregulate Gelatinase Expression in Bone Marrow CD34+ Cells and Their Transmigration Through Reconstituted Basement Membrane Blood, May 15, 1999; 93(10): 3379 - 3390. [Abstract] [Full Text] [PDF]

				R. Navab, E. Chevet, F. Authier, G. M. Di Guglielmo, J. J. M. Bergeron, and P. Brodt Inhibition of Endosomal Insulin-like Growth Factor-I Processing by Cysteine Proteinase Inhibitors Blocks Receptor-mediated Functions J. Biol. Chem., April 20, 2001; 276(17): 13644 - 13649. [Abstract] [Full Text] [PDF]

				P. Brodt, L. Fallavollita, A.-M. Khatib, A. A. Samani, and D. Zhang Cooperative Regulation of the Invasive and Metastatic Phenotypes by Different Domains of the Type I Insulin-like Growth Factor Receptor beta Subunit J. Biol. Chem., August 31, 2001; 276(36): 33608 - 33615. [Abstract] [Full Text] [PDF]

				K. Datta, R. Nambudripad, S. Pal, M. Zhou, H. T. Cohen, and D. Mukhopadhyay Inhibition of Insulin-like Growth Factor-I-mediated Cell Signaling by the von Hippel-Lindau Gene Product in Renal Cancer J. Biol. Chem., June 30, 2000; 275(27): 20700 - 20706. [Abstract] [Full Text] [PDF]