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CHEMOKINE GENE TRANSFECTION INTO TUMOR-CELLS REDUCED TUMORIGENICITY IN NUDE-MICE IN ASSOCIATION WITH NEUTROPHILIC INFILTRATION
Author(s): HIROSE K, HAKOZAKI M, NYUNOYA Y, KOBAYASHI Y, MATSUSHITA K, TAKENOUCHI T, MIKATA A, MUKAIDA N, MATSUSHIMA K
Source: BRITISH JOURNAL OF CANCER    Volume: 72    Issue: 3    Pages: 708-714    Published: SEP 1995  
Times Cited: 65     References: 41     
Abstract: 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-l 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-l, 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-l or mu-MIP-2 did not show any significant difference in growth rate in vivo compared with crones 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.
Document Type: Article
Language: English
Reprint Address: HIROSE, K (reprint author), KUREHA CHEM IND, BIOMED RES INST, SHINJUKU KU, 3-26-2 HYAKUNIN CHO, TOKYO 169, JAPAN
Addresses:
1. TOHO UNIV, FAC SCI, DEPT BIOMOLEC SCI, FUNABASHI, CHIBA 274 JAPAN
2. CHIBA UNIV, SCH MED, DEPT PATHOL 1, CHIBA 280, JAPAN
3. KANAZAWA UNIV, CANC RES INST, DEPT PHARMACOL, KANAZAWA, ISHIKAWA 920 JAPAN
Publisher: STOCKTON PRESS, HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS
Subject Category: Oncology
IDS Number: RT006
ISSN: 0007-0920
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