Oncogenic properties of apoptotic tumor cells in aggressive B cell lymphoma.
Oncogenic properties of apoptotic tumor cells in aggressive B cell lymphoma.
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DOI：
10.1016/j.cub.2014.12.059
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发表时间：
2015-03-02
期刊：
影响因子：
9.2
通讯作者：
Gregory, Christopher D.
中科院分区：
文献类型：
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作者：
Ford, Catriona A.;Petrova, Sofia;Pound, John D.;Voss, Jorine J. L. P.;Melville, Lynsey;Paterson, Margaret;Farnworth, Sarah L.;Gallimore, Awen M.;Cuff, Simone;Wheadon, Helen;Dobbin, Edwina;Ogden, Carol Anne;Dumitriu, Ingrid E.;Dunbar, Donald R.;Murray, Paul G.;Rucker, Dominik;Allen, Judith E.;Hume, David A.;van Rooijen, Nico;Goodlad, John R.;Freeman, Tom C.;Gregory, Christopher D.
已知经历凋亡的细胞调节其组织微环境。通过作用于吞噬细胞，特别是巨噬细胞，凋亡细胞抑制免疫和炎症反应，并促进营养信号通路。特别是，由于它们可能导致肿瘤细胞死亡，从而阻碍恶性疾病进展，细胞凋亡和肿瘤相关巨噬细胞（TAM）通常与癌症的预后不良有关。我们假设，在恶性疾病的进展中，通过细胞凋亡造成的肿瘤细胞群的组成性损失可能产生肿瘤促进作用。在这里，我们证明了凋亡肿瘤细胞促进协调肿瘤生长，血管生成，并在侵略性B细胞淋巴瘤的TAM的积累。通过无偏见的“原位转录组学”分析-激光捕获的TAM的基因表达谱，以建立其原位激活签名-我们表明，这些细胞被激活，通过多种肿瘤促进修复，营养，血管生成，组织重塑和抗炎途径的信号。我们的研究结果还表明，凋亡淋巴瘤细胞有助于驱动这个签名。此外，我们证明，在诱导细胞凋亡，淋巴瘤细胞不仅激活表达的肿瘤促进基质金属蛋白酶MMP 2和MMP 12的巨噬细胞，但也表达和处理这些MMP直接。最后，使用恶性黑色素瘤模型，我们表明，肿瘤细胞凋亡的致癌潜力超出淋巴瘤。除了其深刻的肿瘤抑制作用外，细胞凋亡还可以促进癌症进展。这些结果对于理解细胞死亡的基本生物学、其在恶性疾病中的作用以及诱导凋亡的抗癌治疗的更广泛后果具有重要意义。凋亡性淋巴瘤细胞促进肿瘤生长、血管生成和TAM积累无偏倚的“原位转录组学”分析显示TAM促进促肿瘤途径凋亡性肿瘤细胞表达和加工基质重塑蛋白凋亡性肿瘤细胞的致癌潜力超出淋巴瘤细胞凋亡和肿瘤相关巨噬细胞（TAM）通常与癌症的不良预后相关。福特等人证明凋亡淋巴瘤细胞可以促进肿瘤生长、血管生成、TAM积累和TAM激活，从而促进癌症进展。这些结果对诱导肿瘤坏死的抗癌疗法具有重要意义。
Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. We hypothesized that, in progression of malignant disease, constitutive loss of a fraction of the tumor cell population through apoptosis could yield tumor-promoting effects. Here, we demonstrate that apoptotic tumor cells promote coordinated tumor growth, angiogenesis, and accumulation of TAMs in aggressive B cell lymphomas. Through unbiased “in situ transcriptomics” analysis—gene expression profiling of laser-captured TAMs to establish their activation signature in situ—we show that these cells are activated to signal via multiple tumor-promoting reparatory, trophic, angiogenic, tissue remodeling, and anti-inflammatory pathways. Our results also suggest that apoptotic lymphoma cells help drive this signature. Furthermore, we demonstrate that, upon induction of apoptosis, lymphoma cells not only activate expression of the tumor-promoting matrix metalloproteinases MMP2 and MMP12 in macrophages but also express and process these MMPs directly. Finally, using a model of malignant melanoma, we show that the oncogenic potential of apoptotic tumor cells extends beyond lymphoma. In addition to its profound tumor-suppressive role, apoptosis can potentiate cancer progression. These results have important implications for understanding the fundamental biology of cell death, its roles in malignant disease, and the broader consequences of apoptosis-inducing anti-cancer therapy. Apoptotic lymphoma cells promote tumor growth, angiogenesis, and TAM accumulation Unbiased “in situ transcriptomics” analysis shows TAMs promote pro-tumor pathways Apoptotic tumor cells express and process matrix remodeling proteins The oncogenic potential of apoptotic tumor cells extends beyond lymphoma Apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. Ford et al. demonstrate apoptotic lymphoma cells can promote tumor growth, angiogenesis, TAM accumulation, and TAM activation to potentiate cancer progression. These results have important implications for apoptosis-inducing anti-cancer therapies.
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影响因子：
7.3
作者：
Li F;Huang Q;Chen J;Peng Y;Roop DR;Bedford JS;Li CY
通讯作者：
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影响因子：
4.4
作者：
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肿瘤相关巨噬细胞的细胞和分子起源。
DOI：
10.1126/science.1252510
发表时间：
2014-05-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
Li MO
DOI：
10.1083/jcb.201004096
发表时间：
2010-06-28
期刊：
The Journal of cell biology
影响因子：
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作者：
Elliott MR;Ravichandran KS
通讯作者：
Ravichandran KS
Caspase 3 介导的癌症放射治疗过程中肿瘤细胞增殖的刺激。
影响因子：
82.9
作者：
通讯作者：
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