Artificial selection for host resistance to tumour growth and subsequent cancer cell adaptations: an evolutionary arms race.
Artificial selection for host resistance to tumour growth and subsequent cancer cell adaptations: an evolutionary arms race.
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DOI：
10.1038/s41416-020-01110-1
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发表时间：
2021-01
影响因子：
8.8
通讯作者：
Gatenby RA
中科院分区：
文献类型：
--
作者：
Ibrahim-Hashim A;Luddy K;Abrahams D;Enriquez-Navas P;Damgaci S;Yao J;Chen T;Bui MM;Gillies RJ;O'Farrelly C;Richards CL;Brown JS;Gatenby RA
癌症的进展由肿瘤种群及其宿主的进化动力学决定。由于癌症与宿主一起死亡，每个新的癌细胞群体都必须重新发明策略，以克服宿主的遗传防御。相比之下，如果肿瘤的发展限制了生殖，宿主物种就会在几代人的时间里进化防御策略。我们通过有意培育免疫缺陷的SCID和免疫活性的Black/6小鼠来研究这种“进化军备竞赛”，以进化出更强的肿瘤抑制。在10代以上，我们注射Lewis肺癌细胞[LL/2-Luc-M38]，并在第11天选择性地培育出肿瘤生长最慢的两个个体。它们的雄性后代是下一轮的宿主。进化的SCID小鼠通过增加间充质的增殖通过生物力学限制抑制肿瘤的生长，进化的Black/6小鼠通过增加免疫介导的癌细胞杀伤来抑制肿瘤的生长。然而，多细胞组织和功能基因的转录改变使LL/2-Luc-M38细胞能够通过增加SCID小鼠的基质重塑来适应，并减少了Black/6小鼠的血管生成，增加了能量利用，并加速了增殖。宿主物种可以迅速进化出免疫和非免疫肿瘤防御系统。然而，癌细胞的可塑性允许有效的表型和基于人群的对抗策略。
Cancer progression is governed by evolutionary dynamics in both the tumour population and its host. Since cancers die with the host, each new population of cancer cells must reinvent strategies to overcome the host’s heritable defences. In contrast, host species evolve defence strategies over generations if tumour development limits procreation. We investigate this “evolutionary arms race” through intentional breeding of immunodeficient SCID and immunocompetent Black/6 mice to evolve increased tumour suppression. Over 10 generations, we injected Lewis lung mouse carcinoma cells [LL/2-Luc-M38] and selectively bred the two individuals with the slowest tumour growth at day 11. Their male progeny were hosts in the subsequent round. The evolved SCID mice suppressed tumour growth through biomechanical restriction from increased mesenchymal proliferation, and the evolved Black/6 mice suppressed tumour growth by increasing immune-mediated killing of cancer cells. However, transcriptomic changes of multicellular tissue organisation and function genes allowed LL/2-Luc-M38 cells to adapt through increased matrix remodelling in SCID mice, and reduced angiogenesis, increased energy utilisation and accelerated proliferation in Black/6 mice. Host species can rapidly evolve both immunologic and non-immunologic tumour defences. However, cancer cell plasticity allows effective phenotypic and population-based counter strategies.
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影响因子：
64.8
作者：
Greaves, Mel;Maley, Carlo C.
通讯作者：
Maley, Carlo C.
DOI：
10.1073/pnas.1031601100
发表时间：
2003-05-27
影响因子：
11.1
作者：
Cui, Z;Willingham, MC;DeLong, CJ
通讯作者：
DeLong, CJ
影响因子：
4.2
作者：
Blumberg, D
通讯作者：
Blumberg, D
胰腺导管腺癌的脱木质。
DOI：
10.1016/j.cgh.2009.07.039
发表时间：
2009-11
期刊：
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
影响因子：
--
作者：
Pandol S;Edderkaoui M;Gukovsky I;Lugea A;Gukovskaya A
通讯作者：
Gukovskaya A
影响因子：
7.3
作者：
Foley K;Rucki AA;Xiao Q;Zhou D;Leubner A;Mo G;Kleponis J;Wu AA;Sharma R;Jiang Q;Anders RA;Iacobuzio-Donahue CA;Hajjar KA;Maitra A;Jaffee EM;Zheng L
通讯作者：
Zheng L