Expression of the chemokines IP-10 and Mig in IL-10 transduced tumors.

Abstract

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: H Sun, N Kundu, R Dorsey, M J Jackson, A M Fulton
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) 2001 Mar-Apr Vol. 24 Issue 2 Pg. 138-43 ISSN: 1524-9557 [Print] United States
• PMID: 11265771 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CXCL9 protein, human
• Chemokine CXCL10
• Chemokine CXCL9
• Chemokines, CXC
• Cxcl10 protein, mouse
• Intercellular Signaling Peptides and Proteins
• Lipopolysaccharides
• Monokines
• RNA, Messenger
• RNA, Neoplasm
• Interleukin-10
• Interferon-gamma

Topics

• Animals
• Blotting, Northern
• CD4-Positive T-Lymphocytes (pathology)
• CD8-Positive T-Lymphocytes (pathology)
• Chemokine CXCL10
• Chemokine CXCL9
• Chemokines, CXC (genetics)
• Gene Expression
• Humans
• Immunohistochemistry
• Intercellular Signaling Peptides and Proteins
• Interferon-gamma (pharmacology)
• Interleukin-10 (genetics)
• Kinetics
• Lipopolysaccharides (pharmacology)
• Mammary Neoplasms, Experimental (immunology, metabolism)
• Mice
• Monokines (genetics)
• Neoplasm Transplantation
• RNA, Messenger (analysis)
• RNA, Neoplasm (isolation & purification)
• Transfection
• Tumor Cells, Cultured