help button home button Am J Pathol Angiogenesis Meeting
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kataoka, H.
Right arrow Articles by Koono, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kataoka, H.
Right arrow Articles by Koono, M.
(American Journal of Pathology. 1999;154:457-468.)
© 1999 American Society for Investigative Pathology

Regular Articles

Enhanced Tumor Growth and Invasiveness in Vivo by a Carboxyl-Terminal Fragment of {alpha}1-Proteinase Inhibitor Generated by Matrix Metalloproteinases

A Possible Modulatory Role in Natural Killer Cytotoxicity

Hiroaki Kataoka* , Hirofumi Uchino* , Takeshi Iwamura{dagger} , Motoharu Seiki{ddagger} , Kazuki Nabeshima* and Masashi Koono*

From the Second Department of Pathology* and First Department of Surgery,{dagger} Miyazaki Medical College, Miyazaki, Japan, and the Department of Cancer Cell Research,{ddagger} The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

Matrix metalloproteinases (MMPs) are believed to contribute to the complex process of cancer progression. They also exhibit an {alpha}1-proteinase inhibitor ({alpha}PI)-degrading activity generating a carboxyl-terminal fragment of ~5 kd ({alpha}PI-C). This study reports that overexpression of {alpha}PI-C in S2–020, a cloned subline derived from the human pancreas adenocarcinoma cell line SUIT-2, potentiates the growth capability of the cells in nude mice. After stable transfection of a vector containing a chimeric cDNA encoding a signal peptide sequence of tissue inhibitor of metalloproteinase-1 followed by cDNA for {alpha}PI-C into S2–020 cells, three clones that stably secrete {alpha}PI-C were obtained. The ectopic expression of {alpha}PI-C did not alter in vitro cellular growth. However, subcutaneous injection of the {alpha}PI-C-secreting clones resulted in tumors that were 1.5 to 3-fold larger than those of control clones with an increased tendency to invasiveness and lymph node metastasis. These effects could be a result of modulation of natural killer (NK) cell-mediated control of tumor growth in nude mice, as the growth advantage of {alpha}PI-C-secreting clones was not observed in NK-depleted mice, and {alpha}PI-C-secreting clones showed decreased NK sensitivity in vitro. In addition, production of {alpha}PI and generation of the cleaved form of {alpha}PI by MMP were observed in various human tumor cell lines and in a highly metastatic subline of SUIT-2 in vitro. These results provide experimental evidence that the {alpha}PI-degrading activity of MMPs may play a role in tumor progression not only via the inactivation of {alpha}PI but also via the generation of {alpha}PI-C.




This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
S. V. de Sa, M. L. Correa-Giannella, M. C. Machado, K. Krogh, M. Q. de Almeida, M. A. Albergaria Pereira, S. A. Coelho Siqueira, R. A. Patzina, F. S. Ibuki, M. C. Sogayar, et al.
Serpin Peptidase Inhibitor Clade A Member 1 as a Potential Marker for Malignancy in Insulinomas
Clin. Cancer Res., September 15, 2007; 13(18): 5322 - 5330.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
G Capurso, S Lattimore, T Crnogorac-Jurcevic, F Panzuto, M Milione, V Bhakta, N Campanini, S M Swift, C Bordi, G D. Fave, et al.
Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets.
Endocr. Relat. Cancer, June 1, 2006; 13(2): 541 - 558.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Buchholz, A. Biebl, A. Neesse, M. Wagner, T. Iwamura, G. Leder, G. Adler, and T. M. Gress
SERPINE2 (Protease Nexin I) Promotes Extracellular Matrix Production and Local Invasion of Pancreatic Tumors in Vivo
Cancer Res., August 15, 2003; 63(16): 4945 - 4951.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
N. Devoogdt, G. Hassanzadeh Ghassabeh, J. Zhang, L. Brys, P. De Baetselier, and H. Revets
Secretory leukocyte protease inhibitor promotes the tumorigenic and metastatic potential of cancer cells
PNAS, May 13, 2003; 100(10): 5778 - 5782.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. V. Rozanov, B. Ghebrehiwet, T. I. Postnova, A. Eichinger, E. I. Deryugina, and A. Y. Strongin
The Hemopexin-like C-terminal Domain of Membrane Type 1 Matrix Metalloproteinase Regulates Proteolysis of a Multifunctional Protein, gC1qR
J. Biol. Chem., March 8, 2002; 277(11): 9318 - 9325.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
D. K. Madtes, A. L. Elston, L. A. Kaback, and J. G. Clark
Selective Induction of Tissue Inhibitor of Metalloproteinase-1 in Bleomycin-Induced Pulmonary Fibrosis
Am. J. Respir. Cell Mol. Biol., May 1, 2001; 24(5): 599 - 607.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
F. Moraga and S. Janciauskiene
Activation of Primary Human Monocytes by the Oxidized Form of alpha 1-Antitrypsin
J. Biol. Chem., March 10, 2000; 275(11): 7693 - 7700.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
S. D. Shapiro and R. M. Senior
Matrix Metalloproteinases . Matrix Degradation and More
Am. J. Respir. Cell Mol. Biol., June 1, 1999; 20(6): 1100 - 1102.
[Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1999 by the American Society for Investigative Pathology.