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Microencapsulated iNOS‐expressing cells cause tumor suppression in mice
Author(s) -
Xu Weiming,
Liu Lizhi,
Charles Ian G.
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0590fje
Subject(s) - peroxynitrite , nitric oxide , nitric oxide synthase , chemistry , reactive nitrogen species , cancer cell , cell culture , cancer research , reactive oxygen species , microbiology and biotechnology , biology , biochemistry , cancer , superoxide , enzyme , genetics , organic chemistry
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.