Microencapsulated iNOS-expressing cells cause tumor suppression in mice.

Abstract	Macrophages can kill tumor cells by releasing high levels of nitric oxide (NO) and related reactive nitrogen species such as nitroxyl and peroxynitrite, after up-regulation of expression of the inducible nitric oxide synthase gene (iNOS). In this paper we describe two novel human cell lines that are capable of expressing high levels of iNOS under the control of analogues of either the insect hormone ecdysone or tetracycline. We have entrapped these iNOS-expressing cells within a semipermeable alginate-poly-L-lysine membrane as a means of delivery to tumor sites in a nude mouse model. These encapsulated cells can be induced to generate sustainable high concentrations NO and reactive nitrogen species at tumor sites after treatment either with ponasterone A or muristerone A or with doxycycline. Delivery of these iNOS-expressing cells to tumors formed from human ovarian cancer SKOV-3 cells results in 100% killing, whereas treatment of tumors formed from human colon cancer DLD-1 cells results in 54% killing. We show that in these iNOS-expressing cells, tumor killing is associated with concomitant up-regulation of the Fas/FasL proteins.
Authors	Weiming Xu, Lizhi Liu, Ian G Charles
Journal	FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 16 Issue 2 Pg. 213-5 (Feb 2002) ISSN: 1530-6860 [Electronic] United States
PMID	11772948 (Publication Type: Journal Article)
Chemical References	Alginates Anti-Bacterial Agents alginate-polylysine-alginate Polylysine NOS2 protein, human Nitric Oxide Synthase Nitric Oxide Synthase Type II Nos2 protein, mouse Tetracycline Doxycycline
Topics	Alginates Animals Anti-Bacterial Agents (pharmacology) Cell Line Doxycycline (pharmacology) Female Gene Expression Regulation, Enzymologic Humans Mice Mice, Nude Neoplasm Transplantation Neoplasms, Experimental (enzymology, genetics, therapy) Nitric Oxide Synthase (genetics, metabolism) Nitric Oxide Synthase Type II Polylysine (analogs & derivatives) Tetracycline (pharmacology) Tumor Cells, Cultured Xenograft Model Antitumor Assays

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