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PMID: 7937875 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Endothelial cell implantation and survival within experimental gliomas.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 21 ·1994-10-11 ·Pages 9695-9

Lal B, Indurti RR, Couraud PO, Goldstein GW, Laterra J

Abstract

The delivery of therapeutic genes to primary brain neoplasms opens new opportunities for treating these frequently fatal tumors. Efficient gene delivery to tissues remains an important obstacle to therapy, and this problem has unique characteristics in brain tumors due to the blood-brain and blood-tumor barriers. The presence of endothelial mitogens and vessel proliferation within solid tumors suggests that genetically modified endothelial cells might efficiently transplant to brain tumors. Rat brain endothelial cells immortalized with the adenovirus E1A gene and further modified to express the beta-galactosidase reporter were examined for their ability to survive implantation to experimental rat gliomas. Rats received 9L, F98, or C6 glioma cells in combination with endothelial cells intracranially to caudate/putamen or subcutaneously to flank. Implanted endothelial cells were identified by beta-galactosidase histochemistry or by polymerase chain reaction in all tumors up to 35 days postimplantation, the latest time examined. Implanted endothelial cells appeared to cooperate in tumor vessel formation and expressed the brain-specific endothelial glucose transporter type 1 as identified by immunohistochemistry. The proliferation of implanted endothelial cells was supported by their increased number within tumors between postimplantation days 14 and 21 (P = 0.015) and by their expression of the proliferation antigen Ki67. These findings establish that genetically modified endothelial cells can be stably engrafted to growing gliomas and suggest that endothelial cell implantation may provide a means of delivering therapeutic genes to brain neoplasms and other solid tumors. In addition, endothelial implantation to brain may be useful for defining mechanisms of brain-specific endothelial differentiation.

Related Genes
E1A
MeSH Terms
Adenovirus E1A Proteins/analysis,biosynthesis Animals Base Sequence Brain Neoplasms/pathology Caudate Nucleus Cell Line Cell Survival Cell Transplantation DNA Primers Endothelium, Vascular/cytology Genes, Viral Genetic Therapy/methods Glioma/pathology Molecular Sequence Data Polymerase Chain Reaction Putamen Rats Rats, Inbred F344 Repetitive Sequences, Nucleic Acid beta-Galactosidase/analysis,biosynthesis
Chemicals
Adenovirus E1A Proteins DNA Primers beta-Galactosidase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Lal B
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Indurti R R
Couraud P O
Goldstein G W
Laterra J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.21.9695
Published
1994-10-11
Pages
9695-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC44883
Subset
IM
Grants
NCI NIH HHS · CA06973 · United States
NIEHS NIH HHS · ES02380 · United States
NINDS NIH HHS · NS31081 · United States
External Links
PubMed source DOI: 10.1073/pnas.91.21.9695 PMC Full Text View journal details
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