Chemokine gene transfection into tumour cells reduced tumorigenicity in nude mice in association with neutrophilic infiltration.

Chemokine gene transfection into tumour cells reduced tumorigenicity in nude mice in association with neutrophilic infiltration.
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DOI:
10.1038/bjc.1995.398
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发表时间:
1995-09
影响因子:
8.8
通讯作者:
Matsushima, K.
Matsushima, K.
中科院分区:
医学1区
文献类型:
--
作者:
Hirose, K.;Hakozaki, M.;Nyunoya, Y.;Kobayashi, Y.;Matsushita, K.;Takenouchi, T.;Mikata, A.;Mukaida, N.;Matsushima, K.

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为了研究趋化因子的局部分泌对肿瘤生长的影响,我们通过哺乳动物表达载体将人(mu)白细胞介素8 (IL-8)、人-MCP-1 (MCAF)、人- mip -1 α (LD78)、鼠(mu)-MCP-1 (JE)、人- mip -1 α或人- mip -2基因导入中国仓鼠卵巢(CHO)细胞,并对转染后的细胞在体内形成肿瘤的能力进行了评价。通过转染的克隆产生的hu-IL-8、hu-MIP-1 α或mu-MIP-1 α在体外不影响生长速率,但在裸鼠皮下注射(s.c.)时显著抑制肿瘤生长。然而,转染hu-MCP-1、mu-MCP-1或mu-MIP-2的克隆与单独转染载体的克隆相比,在体内的生长速度没有显著差异。转染hu-IL-8、hu-MIP-1 α或mu-MIP-1 α的CHO克隆注射部位的组织学检查显示以中性粒细胞浸润为主。这些结果表明,趋化因子在肿瘤部位释放时具有强大的抗肿瘤活性,即使是低剂量,这可能是由中性粒细胞募集和靶向趋化因子释放细胞介导的。我们的研究强调了局部趋化因子分泌在诱导强效宿主抗肿瘤防御反应中的潜在作用。
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.
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