Cell fusion potentiates tumor heterogeneity and reveals circulating hybrid cells that correlate with stage and survival.
Cell fusion potentiates tumor heterogeneity and reveals circulating hybrid cells that correlate with stage and survival.
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DOI：
10.1126/sciadv.aat7828
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发表时间：
2018-09
期刊：
影响因子：
13.6
通讯作者：
Wong MH
中科院分区：
文献类型：
--
作者：
Gast CE;Silk AD;Zarour L;Riegler L;Burkhart JG;Gustafson KT;Parappilly MS;Roh-Johnson M;Goodman JR;Olson B;Schmidt M;Swain JR;Davies PS;Shasthri V;Iizuka S;Flynn P;Watson S;Korkola J;Courtneidge SA;Fischer JM;Jaboin J;Billingsley KG;Lopez CD;Burchard J;Gray J;Coussens LM;Sheppard BC;Wong MH
在癌症患者中发现的外周血MФ-cancer细胞融合杂种与疾病分期和总体生存相关。与转移性癌症相关的高致死率凸显了迫切的医学需求，即提高对驱动转移扩散的生物学机制的理解，以及识别预测晚期进展的生物标志物。许多肿瘤细胞的内在和外在机制促进肿瘤的进展；然而，在实体瘤中驱动肿瘤细胞异质性的机制仍然不清楚。应激环境下肿瘤细胞突变率的增加与肿瘤异质性的所有方面有关，但不能解释。我们提供的证据表明，肿瘤细胞与白细胞（如巨噬细胞）的融合有助于肿瘤的异质性，导致细胞表现出增加的转移行为。融合杂交种（具有造血和上皮性质的细胞）在细胞培养和荷瘤小鼠中很容易检测到。此外，人类癌症患者外周血中列举的杂交体与疾病分期相关，并预测总体生存。这种独特的肿瘤细胞群为肿瘤分期提供了一种新的生物标志物，也为干预提供了潜在的治疗靶点。
Peripheral blood MФ–cancer cell fusion hybrids identified in cancer patients correlate with disease stage and overall survival. High lethality rates associated with metastatic cancer highlight an urgent medical need for improved understanding of biologic mechanisms driving metastatic spread and identification of biomarkers predicting late-stage progression. Numerous neoplastic cell intrinsic and extrinsic mechanisms fuel tumor progression; however, mechanisms driving heterogeneity of neoplastic cells in solid tumors remain obscure. Increased mutational rates of neoplastic cells in stressed environments are implicated but cannot explain all aspects of tumor heterogeneity. We present evidence that fusion of neoplastic cells with leukocytes (for example, macrophages) contributes to tumor heterogeneity, resulting in cells exhibiting increased metastatic behavior. Fusion hybrids (cells harboring hematopoietic and epithelial properties) are readily detectible in cell culture and tumor-bearing mice. Further, hybrids enumerated in peripheral blood of human cancer patients correlate with disease stage and predict overall survival. This unique population of neoplastic cells provides a novel biomarker for tumor staging, as well as a potential therapeutic target for intervention.
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影响因子：
3.7
作者：
LaBerge GS;Duvall E;Grasmick Z;Haedicke K;Pawelek J
通讯作者：
Pawelek J
影响因子：
11.2
作者：
Lu X;Kang Y
通讯作者：
Kang Y
影响因子：
64.8
作者：
Alvarez-Dolado, M;Pardal, R;Alvarez-Buylla, A
通讯作者：
Alvarez-Buylla, A
影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I
DOI：
10.1073/pnas.1320198111
发表时间：
2014-03-04
影响因子：
11.1
作者：
Adams, Daniel L.;Martin, Stuart S.;Cristofanilli, Massimo
通讯作者：
Cristofanilli, Massimo