help button home button Am J Pathol ASIP WHAT IS IT?
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 Related articles in Am J Pathol
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 Giannelli, G.
Right arrow Articles by Antonaci, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Giannelli, G.
Right arrow Articles by Antonaci, S.
(American Journal of Pathology. 2002;161:183-193.)
© 2002 American Society for Investigative Pathology

Regular Articles

Transforming Growth Factor-ß1 Triggers Hepatocellular Carcinoma Invasiveness via {alpha}3ß1 Integrin

Gianluigi Giannelli*, Emilia Fransvea*, Felice Marinosci*, Carlo Bergamini*, Silvia Colucci{dagger}, Oronzo Schiraldi* and Salvatore Antonaci*

From the Department of Internal Medicine, Immunology, and Infectious Diseases,*Section of Internal Medicine, and the Department of Human Anatomy and Histology,{dagger}University of Bari Medical School, Bari, Italy

Metastasis occurrence in the course of hepatocellular carcinoma (HCC) severely affects prognosis and survival. We have shown that HCC invasive cells express {alpha}3ß1-integrin whereas noninvasive cells do not. Here we show that transforming growth factor (TGF)-ß1 stimulates {alpha}3-integrin expression at a transcriptional level in noninvasive HCC cells, causing transformation into a motile and invasive phenotype. Such activities are inhibited by neutralizing anti-{alpha}3- but not anti-{alpha}6-integrin monoclonal antibodies. HCC invasive cells secrete abundant levels of active TGF-ß1 in comparison with noninvasive cells, but in the latter, addition of active matrix metalloproteinases-2 increases the concentration of active TGF-ß1. In this way, the cells express {alpha}3-integrin at a transcriptional level and acquire motility on Ln-5. By contrast, an anti-TGF-ß1-neutralizing antibody reduces {alpha}3-integrin expression and the invasive ability of HCC invading cells. In HCC patients, TGF-ß1 serum concentrations and {alpha}3-integrin expression are strongly correlated. The integrin, absent in normal and peritumoral liver parenchyma, is abundantly expressed in HCC primary and metastatic tissue. In particular, patients with metastasis show higher levels of TGF-ß1 serum concentrations and stronger expression of TGF-ß1 and {alpha}3-integrin in HCC tissues. In conclusion, TGF-ß1 may play an important role in HCC invasiveness by stimulating {alpha}3-integrin expression, and could therefore be an important target for new therapies.


Related articles in Am J Pathol:

This Month in AJP

Am J Pathol 2002 161: 1-2. [Full Text]  



This article has been cited by other articles:


Home page
 Exp. Biol. Med.Home page
J. Tang, Y.-M. Wu, P. Zhao, J.-L. Jiang, and Z.-N. Chen
{beta}ig-h3 Interacts with {alpha}3{beta}1 Integrin to Promote Adhesion and Migration of Human Hepatoma Cells
Experimental Biology and Medicine, January 1, 2009; 234(1): 35 - 39.
[Abstract] [Full Text] [PDF]

Home page
 INT J SURG PATHOLHome page
E. S. de Souza Andrade, M. C. d. C. Miguel, R. de Almeida Freitas, L. Pereira Pinto, and L. Batista de Souza
Immunoexpression of Integrins in Ameloblastoma, Adenomatoid Odontogenic Tumor, and Human Tooth Germs
International Journal of Surgical Pathology, July 1, 2008; 16(3): 277 - 285.
[Abstract] [PDF]

Home page
 Cancer Res.Home page
D. C. Lee, Y. K. Kang, W. H. Kim, Y. J. Jang, D. J. Kim, I. Y. Park, B. H. Sohn, H. A. Sohn, H. G. Lee, J. S. Lim, et al.
Functional and Clinical Evidence for NDRG2 as a Candidate Suppressor of Liver Cancer Metastasis
Cancer Res., June 1, 2008; 68(11): 4210 - 4220.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. Zhang, H.-C. Sun, Y. Xu, K.-Z. Zhang, L. Wang, L.-X. Qin, W.-Z. Wu, Y.-K. Liu, S.-L. Ye, and Z.-Y. Tang
Overexpression of Platelet-Derived Growth Factor Receptor {alpha} in Endothelial Cells of Hepatocellular Carcinoma Associated with High Metastatic Potential
Clin. Cancer Res., December 15, 2005; 11(24): 8557 - 8563.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
A. N.M. Fischer, B. Herrera, M. Mikula, V. Proell, E. Fuchs, J. Gotzmann, R. Schulte-Hermann, H. Beug, and W. Mikulits
Integration of Ras subeffector signaling in TGF-{beta} mediated late stage hepatocarcinogenesis
Carcinogenesis, May 1, 2005; 26(5): 931 - 942.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
R. L. Elliott and G. C. Blobe
Role of Transforming Growth Factor Beta in Human Cancer
J. Clin. Oncol., March 20, 2005; 23(9): 2078 - 2093.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Yang, M. Zeisberg, J. C. Lively, P. Nyberg, N. Afdhal, and R. Kalluri
Integrin {alpha}1{beta}1 and {alpha}2{beta}1 Are the Key Regulators of Hepatocarcinoma Cell Invasion Across the Fibrotic Matrix Microenvironment
Cancer Res., December 1, 2003; 63(23): 8312 - 8317.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. Giannelli, E. Fransvea, C. Bergamini, F. Marinosci, and S. Antonaci
Laminin-5 Chains Are Expressed Differentially in Metastatic and Nonmetastatic Hepatocellular Carcinoma
Clin. Cancer Res., September 1, 2003; 9(10): 3684 - 3691.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. Cheng and D. H. Lovett
Gelatinase A (MMP-2) Is Necessary and Sufficient for Renal Tubular Cell Epithelial-Mesenchymal Transformation
Am. J. Pathol., June 1, 2003; 162(6): 1937 - 1949.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2002 by the American Society for Investigative Pathology.