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 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 Abe, R.
Right arrow Articles by Shimizu, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Abe, R.
Right arrow Articles by Shimizu, H.
(American Journal of Pathology. 2004;164:1225-1232.)
© 2004 American Society for Investigative Pathology

Overexpression of Pigment Epithelium-Derived Factor Decreases Angiogenesis and Inhibits the Growth of Human Malignant Melanoma Cells in Vivo

Riichiro Abe*, Tadamichi Shimizu*, Sho-ichi Yamagishi{dagger}, Akihiko Shibaki*, Shinjiro Amano{dagger}, Yosuke Inagaki{dagger}, Hirokazu Watanabe*, Hiroshi Sugawara*, Hideki Nakamura*, Masayoshi Takeuchi{ddagger}, Tsutomu Imaizumi{dagger} and Hiroshi Shimizu*

From the Department of Dermatology,* Hokkaido University Graduate School of Medicine, Sapporo; the Department of Medicine,{dagger} Kurume University School of Medicine, Kurume; and the Department of Biochemistry,{ddagger} Faculty of Pharmaceutical Science, Hokuriku University, Kanazawa, Japan

Pigment epithelium-derived factor (PEDF) has recently been shown to be the most potent inhibitor of angiogenesis in the mammalian eye, and is involved in the pathogenesis of angiogenic eye disease such as proliferative diabetic retinopathy. However, a functional role for PEDF in tumor growth and angiogenesis remains to be determined. In this study, we have investigated both the in vitro and in vivo growth characteristics of human malignant melanoma G361 cell lines, stably transfected to overexpress human PEDF. Expression levels of PEDF proteins in melanoma cell lines G361 and A375 were comparable with that of human cultured melanocytes, whereas vascular endothelial growth factor levels in two tumor cell lines were much stronger than that in normal melanocytes. Overexpression of PEDF was found to significantly inhibit tumor growth and vessel formation in G361 nude mice xenografts. Furthermore, in vitro proliferation rates of G361 cells were decreased in PEDF-transfected cells. PEDF proteins showed dose-dependent induced growth retardation and apoptotic cell death in nontransfected G361 cells, which were completely prevented by treatment with antibodies against the Fas ligand. Our present study highlights two beneficial effects of PEDF treatment on melanoma growth and expansion; one is the suppression of tumor angiogenesis, and the other is induction of Fas ligand-dependent apoptosis in tumor cells. PEDF therefore might be a promising novel therapeutic agent for treatment of patients with melanoma.




This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
T.-C. Ho, S.-L. Chen, Y.-C. Yang, C.-L. Liao, H.-C. Cheng, and Y.-P. Tsao
PEDF induces p53-mediated apoptosis through PPAR gamma signaling in human umbilical vein endothelial cells
Cardiovasc Res, November 1, 2007; 76(2): 213 - 223.
[Abstract] [Full Text] [PDF]

Home page
 J. Dent. Res.Home page
C.R. Dass, T.M.N. Tran, and P.F.M. Choong
Angiogenesis Inhibitors and the Need for Anti-angiogenic Therapeutics
J. Dent. Res., October 1, 2007; 86(10): 927 - 936.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
L. W. T. Cheung, S. C. L. Au, A. N. Y. Cheung, H. Y. S. Ngan, J. Tombran-Tink, N. Auersperg, and A. S. T. Wong
Pigment Epithelium-Derived Factor Is Estrogen Sensitive and Inhibits the Growth of Human Ovarian Cancer and Ovarian Surface Epithelial Cells
Endocrinology, September 1, 2006; 147(9): 4179 - 4191.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
M. Ushio-Fukai
Redox signaling in angiogenesis: Role of NADPH oxidase
Cardiovasc Res, July 15, 2006; 71(2): 226 - 235.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
E. T.H. Ek, C. R. Dass, and P. F.M. Choong
Pigment epithelium-derived factor: a multimodal tumor inhibitor.
Mol. Cancer Ther., July 1, 2006; 5(7): 1641 - 1646.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
G. Maik-Rachline and R. Seger
Variable phosphorylation states of pigment-epithelium-derived factor differentially regulate its function
Blood, April 1, 2006; 107(7): 2745 - 2752.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Filleur, K. Volz, T. Nelius, Y. Mirochnik, H. Huang, T. A. Zaichuk, M. S. Aymerich, S. P. Becerra, R. Yap, D. Veliceasa, et al.
Two Functional Epitopes of Pigment Epithelial-Derived Factor Block Angiogenesis and Induce Differentiation in Prostate Cancer
Cancer Res., June 15, 2005; 65(12): 5144 - 5152.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. Nyberg, L. Xie, and R. Kalluri
Endogenous Inhibitors of Angiogenesis
Cancer Res., May 15, 2005; 65(10): 3967 - 3979.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Garcia, N. I. Fernandez-Garcia, V. Rivas, M. Carretero, M. J. Escamez, A. Gonzalez-Martin, E. E. Medrano, O. Volpert, J. L. Jorcano, B. Jimenez, et al.
Inhibition of Xenografted Human Melanoma Growth and Prevention of Metastasis Development by Dual Antiangiogenic/Antitumor Activities of Pigment Epithelium-Derived Factor
Cancer Res., August 15, 2004; 64(16): 5632 - 5642.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2004 by the American Society for Investigative Pathology.