Human prostate sphere-forming cells represent a subset of basal epithelial cells capable of glandular regeneration in vivo.
Human prostate sphere-forming cells represent a subset of basal epithelial cells capable of glandular regeneration in vivo.
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DOI：
10.1002/pros.21083
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发表时间：
2010-04-01
期刊：
影响因子：
2.8
通讯作者：
Witte, Owen N.
中科院分区：
文献类型：
--
作者：
Garraway, Isla P.;Sun, Wenyi;Tran, Chau P.;Perner, Sven;Zhang, Bao;Goldstein, Andrew S.;Hahm, Scott A.;Haider, Maahum;Head, Christian S.;Reiter, Robert E.;Rubin, Mark A.;Witte, Owen N.
前列腺干/祖细胞在腺体发育和维持中的功能。它们可能是肿瘤起始的靶点，因此对这些细胞的表征可能具有治疗意义。在体外形成球体的来自解离组织的细胞通常代表干细胞/祖细胞。在本研究中，评估了形成前列腺球的人类前列腺细胞亚群的自我更新和组织再生能力。从59个前列腺切除术标本中生成前列腺球。通过免疫组织化学和荧光原位杂交（FISH）确定谱系标志物表达和TMPRSS-ERG状态。通过细胞分选分离前列腺上皮细胞亚群，并询问其球体形成活性。通过在免疫功能低下的小鼠中将球形形成细胞与大鼠尿生殖窦间充质（rUGSM）皮下结合来评估组织再生潜力。前列腺组织标本是异质的，包含良性和恶性（Gleason 3-5）腺体。TMPRSS-ERG融合在大约70%的癌症中被发现。前列腺球以可变的比率（0.5-4%）从单细胞发育，并且可以连续传代。在球形形成细胞中观察到基础表型（CD 44 + CD 49 f + CK 5 +p63+ CK 8 −AR−PSA−）。表达肿瘤相关钙信号转导子2（Trop 2）、CD 44和CD 49 f的前列腺细胞亚群优先形成球体。球体形成细胞和rUGSM再生的含有离散基底层和管腔层的管状结构的体内植入。TMPRSS-ERG融合在来自融合阳性肿瘤组织的前列腺球中不存在，表明良性前列腺上皮细胞的存活/生长优势。人前列腺球形成细胞自我更新，具有组织再生能力，并代表基底细胞的亚群。前列腺70：491-501，2010年。© 2009 Wiley-Liss公司。
Prostate stem/progenitor cells function in glandular development and maintenance. They may be targets for tumor initiation, so characterization of these cells may have therapeutic implications. Cells from dissociated tissues that form spheres in vitro often represent stem/progenitor cells. A subset of human prostate cells that form prostaspheres were evaluated for self-renewal and tissue regeneration capability in the present study. Prostaspheres were generated from 59 prostatectomy specimens. Lineage marker expression and TMPRSS-ERG status was determined via immunohistochemistry and fluorescence in situ hybridization (FISH). Subpopulations of prostate epithelial cells were isolated by cell sorting and interrogated for sphere-forming activity. Tissue regeneration potential was assessed by combining sphere-forming cells with rat urogenital sinus mesenchyme (rUGSM) subcutaneously in immunocompromised mice. Prostate tissue specimens were heterogeneous, containing both benign and malignant (Gleason 3–5) glands. TMPRSS-ERG fusion was found in approximately 70% of cancers examined. Prostaspheres developed from single cells at a variable rate (0.5–4%) and could be serially passaged. A basal phenotype (CD44+CD49f+CK5+p63+CK8−AR−PSA−) was observed among sphere-forming cells. Subpopulations of prostate cells expressing tumor-associated calcium signal transducer 2 (Trop2), CD44, and CD49f preferentially formed spheres. In vivo implantation of sphere-forming cells and rUGSM regenerated tubular structures containing discreet basal and luminal layers. The TMPRSS-ERG fusion was absent in prostaspheres derived from fusion-positive tumor tissue, suggesting a survival/growth advantage of benign prostate epithelial cells. Human prostate sphere-forming cells self-renew, have tissue regeneration capability, and represent a subpopulation of basal cells. Prostate 70: 491–501, 2010. © 2009 Wiley-Liss, Inc.
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影响因子：
11.2
作者：
Vander Griend DJ;Karthaus WL;Dalrymple S;Meeker A;DeMarzo AM;Isaacs JT
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影响因子：
10.5
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