Neoplastic reprogramming of patient-derived adipose stem cells by prostate cancer cell-associated exosomes.
Neoplastic reprogramming of patient-derived adipose stem cells by prostate cancer cell-associated exosomes.
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DOI：
10.1002/stem.1619
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发表时间：
2014-04
期刊：
影响因子：
5.2
通讯作者：
Abdel-Mageed, Asim B.
中科院分区：
文献类型：
--
作者：
Abd Elmageed, Zakaria Y.;Yang, Yijun;Thomas, Raju;Ranjan, Manish;Mondal, Debasis;Moroz, Krzysztof;Fang, Zhide;Rezk, Bashir M.;Moparty, Krishnarao;Sikka, Suresh C.;Sartor, Oliver;Abdel-Mageed, Asim B.
新出现的证据表明，间充质干细胞（MSC）经常被招募到肿瘤部位，但它们在肿瘤生长和疾病进展中的功能意义仍然难以捉摸。在此，我们报告了前列腺癌（PC）细胞微环境破坏PC患者脂肪源性干细胞（pASC）进行肿瘤转化。与正常ASCs不同，用PC细胞条件培养基（CM）引发的pASCs在体内形成前列腺样肿瘤病变，并在第二受体中再现侵袭性肿瘤。pASC肿瘤获得了细胞遗传学畸变和间充质-上皮转化（MET），并表达了上皮、肿瘤和血管生成标志物，这些标志物使人联想到PC肿瘤异种移植物的分子特征。我们的机制研究表明，PC细胞衍生的外泌体足以重演由CM引发的pASC在体内产生的前列腺致瘤性拟态的形成。除了大肿瘤抑制因子同源物2（Lats 2）和程序性细胞死亡蛋白4（PDCD 4）（一种肿瘤转化抑制剂）的下调外，pASC的致瘤性重编程与PC细胞来源的致癌因子外泌体的运输相关，所述致癌因子包括H-ras和K-ras转录物、oncomiRNA、miR-125 b、miR-130 b、miR-125 b、miR-130 b和miR-130 b。和miR-155以及GTP酶Rab 1a、Rab 1b和Rab 11 a的Ras超家族。我们的研究结果暗示了PC细胞衍生的外泌体通过癌症患者中肿瘤嗜性ASC的肿瘤重编程在肿瘤克隆扩增中的新作用。
Emerging evidence suggests that mesenchymal stem cells (MSCs) are often recruited to tumor sites but their functional significance in tumor growth and disease progression remains elusive. Herein we report that prostate cancer (PC) cell microenvironment subverts PC patient adipose-derived stem cells (pASCs) to undergo neoplastic transformation. Unlike normal ASCs, the pASCs primed with PC cell conditioned media (CM) formed prostate-like neoplastic lesions in vivo and reproduced aggressive tumors in secondary recipients. The pASC tumors acquired cytogenetic aberrations and mesenchymal-to-epithelial transition (MET) and expressed epithelial, neoplastic, and vasculogenic markers reminiscent of molecular features of PC tumor xenografts. Our mechanistic studies revealed that PC cell-derived exosomes are sufficient to recapitulate formation of prostate tumorigenic mimicry generated by CM-primed pASCs in vivo. In addition to down-regulation of the large tumor suppressor homolog2 (Lats2) and the programmed cell death protein 4 (PDCD4), a neoplastic transformation inhibitor, the tumorigenic reprogramming of pASCs was associated with trafficking by PC cell-derived exosomes of oncogenic factors, including H-ras and K-ras transcripts, oncomiRNAs miR-125b, miR-130b, and miR-155 as well as the Ras superfamily of GTPases Rab1a, Rab1b, and Rab11a. Our findings implicate a new role for PC cell-derived exosomes in clonal expansion of tumors through neoplastic reprogramming of tumor tropic ASCs in cancer patients.
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DOI：
10.1073/pnas.0703942104
发表时间：
2007-10-09
影响因子：
11.1
作者：
Gironella, Meritxell;Seux, Mylene;Dusetti, Nelson J.
通讯作者：
Dusetti, Nelson J.
DOI：
10.1158/1055-9965.epi-11-0556
发表时间：
2011-11
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Bellows CF;Zhang Y;Chen J;Frazier ML;Kolonin MG
通讯作者：
Kolonin MG
影响因子：
5.2
作者：
Klopp, Ann H.;Gupta, Anshul;Spaeth, Erika;Andreeff, Michael;Marini, Frank, III
通讯作者：
Marini, Frank, III
DOI：
10.1073/pnas.0602266103
发表时间：
2006-05-02
影响因子：
11.1
作者：
Costinean, S;Zanesi, N;Croce, CM
通讯作者：
Croce, CM
DOI：
10.1073/pnas.1016611107
发表时间：
2010-12-14
影响因子：
11.1
作者：
Bousquet, Marina;Harris, Marian H.;Lodish, Harvey F.
通讯作者：
Lodish, Harvey F.