Transforming growth factor beta 1 (TGF-beta 1) produced in tumour tissue after chemotherapy acts as a lymphokine-activated killer attractant.
Transforming growth factor beta 1 (TGF-beta 1) produced in tumour tissue after chemotherapy acts as a lymphokine-activated killer attractant.
复制标题
化学疗法后在肿瘤组织中产生的转化生长因子β1（TGF-β1）充当淋巴细胞激活的杀伤剂。
DOI：
10.1038/bjc.1996.351
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发表时间：
1996-07
影响因子：
8.8
通讯作者：
Hosokawa, M
中科院分区：
文献类型：
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作者：
Kuramitsu, Y;Nishibe, M;Kobayashi, M;Togashi, Y;Yuan, L;Takizawa, M;Okada, F;Hosokawa, M
采用琼脂糖迁移（UAM）试验，我们研究了淋巴因子激活的杀伤细胞（LAK）的诱导活性，在培养条件培养基的肿瘤组织化疗后，作为一个可能的机制，增强LAK细胞积累到肿瘤组织化疗后。BMT-11是在C57 BL/6小鼠中发展的纤维肉瘤。从用各种抗癌药物处理的小鼠中获得的BMT-11肿瘤组织的条件培养基对LAK细胞具有趋化活性（LAK-吸引活性）。在未处理的肿瘤组织中观察到白细胞介素（IL）-1 α、IL-6、IL-8、干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α的mRNA表达，环磷酰胺处理未增强这些表达。通过逆转录-聚合酶链反应（RT-PCR）未在未治疗的肿瘤组织中检测到TGF-β 1的mRNA表达，但在环磷酰胺治疗的肿瘤组织中检测到。重组人TGF-β 1在0.1 ng ml-1和1 ng ml-1的浓度下显示出LAK吸引活性，而新鲜脾细胞不被TGF-β 1吸引。抗-TGF-β 1抗体抑制LAK-引诱剂活性的肿瘤组织处理的条件培养基中的环磷酰胺约35%，在100微克ml-1的控制。这些发现表明，在用抗癌药物治疗的小鼠的肿瘤组织中产生的TGF-β 1可能是LAK吸引剂。通过对自然杀伤细胞抗性BMT-11肿瘤细胞进行4 h 51 Cr释放测定，我们观察到TGF-β 1在0.01 ng ml-1至10 ng ml-1的浓度下在效应期不抑制LAK活性。综上所述，我们认为，肿瘤组织中产生的TGF-β 1化疗后参与聚集转移的LAK细胞，并有助于转移的LAK细胞的治疗效果。
Using an under agarose migration (UAM) assay, we studied lymphokine-activated killer (LAK)-attractant activity in cultured conditioned medium of tumour tissues after chemotherapy as a possible mechanism of enhanced LAK cell accumulation into tumour tissues after chemotherapy. BMT-11 is a fibrosarcoma developed in C57BL/6 mice. The conditioned medium of BMT-11 tumour tissues obtained from mice treated with various anti-cancer drugs had chemotactic activity for LAK cells (LAK-attractant activity). mRNA expression of interleukin (IL)-1 alpha, IL-6, IL-8, interferon (IFN)-gamma, and tumour necrosis factor (TNF)-alpha was observed in untreated tumour tissues, which were not enhanced by cyclophosphamide treatment. mRNA expression of TGF-beta 1 was not detected in untreated tumour tissues by reverse transcription-polymerase chain reaction (RT-PCR), but was detected in tumour tissues treated with cyclophosphamide. Recombinant human TGF-beta 1 showed LAK-attractant activity at a concentration of 0.1 ng ml-1 and 1 ng ml-1, whereas fresh splenocytes were not attracted by TGF-beta 1. Anti-TGF-beta 1 antibody inhibited LAK-attractant activity in the conditioned medium of tumour tissues treated with cyclophosphamide to approximately 35% that of control at 100 micrograms ml-1. These findings indicate that TGF-beta 1 produced in the tumour tissues of mice treated with anti-cancer drugs could be a LAK attractant. By a 4 h 51Cr release assay of natural killer cell-resistant BMT-11 tumour cells, we observed that TGF-beta 1 at a concentration from 0.01 ng ml-1 to 10 ng ml-1 did not inhibit LAK activity in an effector phase. Taken together, we suggest that TGF-beta 1 produced in tumour tissues after chemotherapy participates in gathering transferred LAK cells and contributes to the therapeutic effects of transferred LAK cells.