Document Detail


Suppression of angiogenesis, tumorigenicity, and metastasis by human prostate cancer cells engineered to produce interferon-beta.
MedLine Citation:
PMID:  10029078     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We determined whether the IFN-beta gene can be used to suppress angiogenesis, tumor growth, and metastasis of human prostate cancer cells growing in the prostate of nude mice. Highly metastatic PC-3M human prostate cancer cells were engineered to constitutively produce murine IFN-beta subsequent to infection with a retroviral vector containing murine IFN-beta cDNA. Parental (PC-3M-P), control vector-transduced (PC-3M-Neo), and IFN-beta-transduced (PC-3M-IFN-beta) cells were injected into the prostate (orthotopic) or subcutis (ectopic) of nude mice. PC-3M-P and PC-3M-Neo cells produced rapidly growing tumors and regional lymph node metastases, whereas PC-3M-IFN-beta cells did not. PC-3M-IFN-beta cells also suppressed the tumorigenicity of bystander nontransduced prostate cancer cells. PC-3M-IFN-beta cells produced small tumors (3-5 mm in diameter) in nude mice treated with anti-asialo GM1 antibodies and in severe combined immunodeficient/Beige mice. Immunohistochemical staining revealed that PC-3M-IFN-beta tumors were homogeneously infiltrated by macrophages, whereas control tumors contained fewer macrophages at their periphery. Most tumor cells in the control tumors were stained positive by an antibody to proliferative cell nuclear antigen; very few were positively stained by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling. In sharp contrast, PC-3M-IFN-beta tumors contained fewer proliferative cell nuclear antigen-positive cells and many terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling-positive cells. Staining with antibody against CD31 showed that control tumors contained more blood vessels than PC-3M-IFN-beta tumors. PC-3M-IFN-beta cells were more sensitive to lysis mediated by natural killer cells in vitro or to cytostasis mediated by macrophages than control transduced cells. Conditioned medium from PC-3M-IFN-beta cells augmented splenic cell-mediated cytolysis to control tumor cells, which could be neutralized by antibody against IFN-beta. Collectively, the data suggest that the suppression of tumorigenicity and metastasis of PC-3M-IFN-beta cells is due to inhibition of angiogenesis and activation of host effector cells.
Authors:
Z Dong; G Greene; C Pettaway; C P Dinney; I Eue; W Lu; C D Bucana; M D Balbay; D Bielenberg; I J Fidler
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  59     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-03-04     Completed Date:  1999-03-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  872-9     Citation Subset:  IM    
Affiliation:
Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. zdong@notes.mdacc.tmc.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Cytotoxicity, Immunologic
Gene Therapy
Gene Transfer Techniques
Humans
Interferon-beta / genetics*
Killer Cells, Natural / immunology
Macrophages / immunology
Male
Mice
Mice, Nude
Mice, SCID
Neovascularization, Pathologic / prevention & control*
Prostatic Neoplasms / blood supply,  prevention & control*
Grant Support
ID/Acronym/Agency:
CA16672/CA/NCI NIH HHS; R35-CA42107/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
77238-31-4/Interferon-beta

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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