Endothelial Cell Implantation and Survival Within Experimental Gliomas

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1994 Oct 11

PMID 7937875

Citations 6

Authors

B Lal

R R Indurti

P O Couraud

G W GOLDSTEIN

J Laterra

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Ferry N, Duplessis O, Houssin D, Danos O, Heard J . Retroviral-mediated gene transfer into hepatocytes in vivo. Proc Natl Acad Sci U S A. 1991; 88(19):8377-81. PMC: 52511. DOI: 10.1073/pnas.88.19.8377. View

Yao S, Wilson J, Nabel E, Kurachi S, Hachiya H, Kurachi K . Expression of human factor IX in rat capillary endothelial cells: toward somatic gene therapy for hemophilia B. Proc Natl Acad Sci U S A. 1991; 88(18):8101-5. PMC: 52454. DOI: 10.1073/pnas.88.18.8101. View

Rubin L, Hall D, Porter S, Barbu K, Cannon C, Horner H . A cell culture model of the blood-brain barrier. J Cell Biol. 1991; 115(6):1725-35. PMC: 2289219. DOI: 10.1083/jcb.115.6.1725. View

Schinstine M, Kawaja M, Gage F . Intracerebral delivery of growth factors: potential application of genetically modified fibroblasts. Prog Growth Factor Res. 1991; 3(1):57-66. DOI: 10.1016/0955-2235(91)90013-t. View

Guerin C, Laterra J, Drewes L, Brem H, GOLDSTEIN G . Vascular expression of glucose transporter in experimental brain neoplasms. Am J Pathol. 1992; 140(2):417-25. PMC: 1886421. View

Dichek D . Retroviral vector-mediated gene transfer into endothelial cells. Mol Biol Med. 1991; 8(2):257-66. View

Jiao S, Wolff J . Long-term survival of autologous muscle grafts in rat brain. Neurosci Lett. 1992; 137(2):207-10. DOI: 10.1016/0304-3940(92)90405-v. View

Culver K, Ram Z, Wallbridge S, Ishii H, Oldfield E, Blaese R . In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors. Science. 1992; 256(5063):1550-2. DOI: 10.1126/science.1317968. View

Shibuya M, Miwa T, Hoshino T . Embedding and fixation techniques for immunohistochemical staining with anti-DNA polymerase alpha and Ki-67 monoclonal antibodies to analyze the proliferative potential of tumors. Biotech Histochem. 1992; 67(3):161-4. DOI: 10.3109/10520299209110028. View

10.

Plate K, Breier G, Weich H, Risau W . Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature. 1992; 359(6398):845-8. DOI: 10.1038/359845a0. View

11.

Messina L, Podrazik R, Whitehill T, Ekhterae D, Brothers T, Wilson J . Adhesion and incorporation of lacZ-transduced endothelial cells into the intact capillary wall in the rat. Proc Natl Acad Sci U S A. 1992; 89(24):12018-22. PMC: 50689. DOI: 10.1073/pnas.89.24.12018. View

12.

Le Gal la Salle G, Robert J, Berrard S, Ridoux V, Perricaudet M, Mallet J . An adenovirus vector for gene transfer into neurons and glia in the brain. Science. 1993; 259(5097):988-90. DOI: 10.1126/science.8382374. View

13.

DURIEU-TRAUTMANN O, Federici C, Creminon C, Roux F, Claire M, Strosberg A . Nitric oxide and endothelin secretion by brain microvessel endothelial cells: regulation by cyclic nucleotides. J Cell Physiol. 1993; 155(1):104-11. DOI: 10.1002/jcp.1041550114. View

14.

Breakefield X . Gene delivery into the brain using virus vectors. Nat Genet. 1993; 3(3):187-9. DOI: 10.1038/ng0393-187. View

15.

Davidson B, ALLEN E, Kozarsky K, Wilson J, Roessler B . A model system for in vivo gene transfer into the central nervous system using an adenoviral vector. Nat Genet. 1993; 3(3):219-23. DOI: 10.1038/ng0393-219. View

16.

Whitesell L, Geselowitz D, Chavany C, Fahmy B, Walbridge S, Alger J . Stability, clearance, and disposition of intraventricularly administered oligodeoxynucleotides: implications for therapeutic application within the central nervous system. Proc Natl Acad Sci U S A. 1993; 90(10):4665-9. PMC: 46573. DOI: 10.1073/pnas.90.10.4665. View

17.

Roux F, DURIEU-TRAUTMANN O, Chaverot N, Claire M, Mailly P, Bourre J . Regulation of gamma-glutamyl transpeptidase and alkaline phosphatase activities in immortalized rat brain microvessel endothelial cells. J Cell Physiol. 1994; 159(1):101-13. DOI: 10.1002/jcp.1041590114. View

18.

Arosarena O, Guerin C, Brem H, Laterra J . Endothelial differentiation in intracerebral and subcutaneous experimental gliomas. Brain Res. 1994; 640(1-2):98-104. DOI: 10.1016/0006-8993(94)91861-9. View

19.

Lal B, Cahan M, Couraud P, GOLDSTEIN G, Laterra J . Development of endogenous beta-galactosidase and autofluorescence in rat brain microvessels: implications for cell tracking and gene transfer studies. J Histochem Cytochem. 1994; 42(7):953-6. DOI: 10.1177/42.7.8014479. View

20.

Benda P, Lightbody J, Sato G, Levine L, Sweet W . Differentiated rat glial cell strain in tissue culture. Science. 1968; 161(3839):370-1. DOI: 10.1126/science.161.3839.370. View