Chemokine gene transfection into tumour cells reduced tumorigenicity in nude mice in association with neutrophilic infiltration.
To study the effect of localised secretion of chemokines on tumour growth, the genes for human (hu) interleukin 8 (IL-8), hu-MCP-1 (MCAF), hu-MIP-1 alpha (LD78), murine (mu)-MCP-1 (JE), mu-MIP-1 alpha or mu-MIP-2 were introduced, via mammalian expression vectors, into Chinese hamster ovary (CHO) cells, and the ability of transfected cells to form tumours in vivo was evaluated. The production of hu-IL-8, hu-MIP-1 alpha or mu-MIP-1 alpha by transfected clones did not influence the growth rate in vitro, but drastically suppressed tumour growth when injected subcutaneously (s.c.) into nude mice. However, clones transfected with hu-MCP-1, mu-MCP-1 or mu-MIP-2 did not show any significant difference in growth rate in vivo compared with clones transfected with vector alone. Histological examination of the site of injection of CHO clones transfected with hu-IL-8, hu-MIP-1 alpha or mu-MIP-1 alpha showed predominantly neutrophilic infiltration. These results indicate that chemokines have potent anti-tumour activity when released, even at low doses, at the tumour site, which may be mediated by recruitment and targeting of neutrophilic granulocytes to chemokine-releasing cells. Our studies highlight the potential usefulness of localised chemokine secretion in inducing potent host anti-tumour defensive responses.
Hirose
K
K
Biomedical Research Institute, Kureha Chemical Industry, Tokyo, Japan.
Hakozaki
M
M
Nyunoya
Y
Y
Kobayashi
Y
Y
Matsushita
K
K
Takenouchi
T
T
Mikata
A
A
Mukaida
N
N
Matsushima
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells / Q000378:metabolism / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D018932:Chemokine CCL2; D019742:Chemokines, CC; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D006224:Cricetinae; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D019402:Macrophage Inflammatory Proteins; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D010957:Plasmids / Q000235:genetics; D011817:Rabbits; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D014162:Transfection
C095218:Ccl9 protein, mouse; D018932:Chemokine CCL2; D019742:Chemokines, CC; D002630:Chemotactic Factors; D016207:Cytokines; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D011994:Recombinant Proteins