Role of natural killer cells in hormone-independent rapid tumor formation and spontaneous metastasis of breast cancer cells in vivo
Role of natural killer cells in hormone-independent rapid tumor formation and spontaneous metastasis of breast cancer cells in vivo
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DOI：
10.1007/s10549-006-9416-4
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发表时间：
2007-09-01
影响因子：
3.8
通讯作者：
Yamamoto, Naoki
中科院分区：
文献类型：
--
作者：
Dewan, Md. Zahidunnabi;Terunuma, Hiroshi;Yamamoto, Naoki
自然杀伤(NK)细胞在宿主抵抗肿瘤和病毒感染的细胞中起着核心作用。NK细胞在肿瘤生长和转移中的直接作用尚不清楚。在此，我们证明了缺乏T、B和NK细胞的NOD/SCID/Gamma c(Null)(NOG)小鼠接种乳腺癌细胞后，能有效地形成大肿瘤和自发器官转移。而在T、B细胞敲除的NOD/SCID小鼠中，乳腺癌细胞在NK细胞的接种部位产生了一个小的肿瘤，但完全没有转移到各个器官。与未治疗的NOD/SCID小鼠相比，经抗小鼠TM-β1抗体处理的NOD/SCID小鼠的免疫抑制导致肿瘤形成和器官转移增加，该抗体可在体内瞬时消除NK细胞的活性。活化的NK细胞在体内抑制肿瘤生长。乳腺癌细胞在NOG小鼠体内的快速高效植入表明，这种新的动物模型为了解和研究肿瘤细胞生长和转移的机制提供了一个独特的机会。我们的结果表明，NK细胞在肿瘤的生长和转移中起着重要的作用，无论是单独还是与常规治疗相结合，NK细胞都可能成为一种有前途的抗癌免疫治疗策略。
Natural killer (NK) cells play a central role in host defense against tumor and virus-infected cells. Direct role of NK cells in tumor growth and metastasis remains to be elucidated. We here demonstrated that NOD/SCID/gamma c(null) ( NOG) mice lacking T, B and NK cells inoculated with breast cancer cells were efficient in the formation of a large tumor and spontaneous organ-metastasis. In contrast, breast cancer cells produced a small tumor at inoculated site in T and B cell knock-out NOD/SCID mice with NK cells while completely failed to metastasize into various organs. Immunosupression of NOD/SCID by treatment with an anti-murine TM-beta 1 antibody, which transiently abrogates NK cell activity in vivo, resulted in enhancing tumor formation and organ-metastasis in comparison with non-treated NOD/SCID mice. Activated NK cells inhibited tumor growth in vivo. The rapid and efficient engraftment of the breast cancer cells in NOG mice suggests that this new animal model could provide a unique opportunity to understand and investigate the mechanism of tumor cell growth and metastasis. Our results suggest that NK cells play an important role in cancer growth and metastasis and could be a promising immunotherapeutic strategy against cancer either alone or in combination with conventional therapy.