title: Expression of the Chemokines IP-10 and Mig in IL-10 Transduced Tumors.
abstract: SUMMARY: Several laboratories have reported marked tumor inhibition when the cytokine interleukin-10 (IL-10) is overexpressed as a transgene in a variety of tumor cells. To identify critical effector molecules, we compared the expression of the chemokine crg-2, the murine homolog of human inducible protein 10 (human IP-10) in murine mammary tumors derived from the transplantation of six IL-10 expressing clones of tumor cell line 66.1, parental 66.1, or 66-neo-cells. We observed increased levels of IP-10 mRNA in all IL-10-expressing tumors examined in comparison to 66-neo. IP-10 mRNA was not detected in parental 66.1 tumors. The closely related chemokine Mig (monokine induced by interferon-gamma [IFN-gamma]) was also induced in all IL-10-expressing tumors. Studies of cultured tumor cells in vitro show that mammary epithelial tumor cells, in the absence of host elements, can express IP-10 and Mig in response to induction with either lipopolysaccharide (LPS) or IFN-gamma alone. The combination of LPS plus IFN-gamma resulted in even greater induction of IP-10 RNA. The kinetics of induction differ somewhat for the two chemokines, with IP-10 showing slower induction and less rapid decline. Because both Mig and IP-10 are chemotactic for tumor-infiltrating lymphocytes, we examined the presence of CD4+ and CD8+ lymphocytes in these tumors. Consistent with the upregulation of Mig and IP-10, we saw significantly increased numbers of CD8+ cells and a lesser increase in CD4+ cells in tumors with elevated levels of both chemokines.
authors.affiliation: Greenebaum Cancer Center and Departments of Pathology and Neurology, University of Maryland and Department of Molecular Biology and Biophysics, University of Maryland Medical Biotechnology Center, Baltimore, Maryland, U.S.A.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Namita
authors.initials: N
authors.lastname: Kundu
authors.forename: Russell
authors.initials: R
authors.lastname: Dorsey
authors.forename: Marion J.
authors.initials: MJ
authors.lastname: Jackson
authors.forename: Amy M.
authors.initials: AM
authors.lastname: Fulton