Microvesicle induction of prostate specific gene expression in normal human bone marrow cells.
Microvesicle induction of prostate specific gene expression in normal human bone marrow cells.
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DOI：
10.1016/j.juro.2010.06.119
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发表时间：
2010-11
期刊：
影响因子：
--
通讯作者：
Quesenberry P
中科院分区：
文献类型：
--
作者：
Renzulli JF 2nd;Del Tatto M;Dooner G;Aliotta J;Goldstein L;Dooner M;Colvin G;Chatterjee D;Quesenberry P
遗传物质通过微泡从癌细胞转移到正常细胞。细胞特异性表型可以在正常细胞中通过微泡中的物质转移而诱导，从而导致遗传变化。我们报道在与人前列腺癌细胞共培养的正常人骨髓细胞中鉴定和表达前列腺特异性基因。我们采集了11位前列腺癌患者的前列腺组织。4例前列腺组织与人骨髓共培养2天或7天，用0.4 μM聚苯乙烯膜将其分离。在5例患者肿瘤组织中收集条件培养基并进行超离心，收集微囊泡进行共培养(3)和囊泡表征(3)。从培养物中收获外植的人骨髓并提取RNA。选择前列腺特异性基因进行实时逆转录聚合酶链反应。分别有4例和3例骨髓暴露于人前列腺肿瘤或分离的微泡培养中，其前列腺基因表达至少是对照骨髓的2倍或更高。正常前列腺共培养1例，正常骨髓无前列腺基因增高。前列腺癌肿瘤细胞与人骨髓细胞共培养可诱导前列腺特异性基因表达。提出的遗传物质转移的机制是通过微泡。这为新型治疗剂（如抗体）提供了一个机会，可以阻止癌细胞释放微囊泡或阻止细胞接受微囊泡。
Transfer of genetic material from cancer cells to normal cells occurs via microvesicles. Cell specific phenotypes can be induced in normal cells by the transfer of material in microvesicles, leading to genetic changes. We report the identification and expression of prostate specific genes in normal human marrow cells co-cultured with human prostate cancer cells. We harvested prostate tissue from 11 patients with prostate cancer. In 4 cases prostate tissue was co-cultured across from human marrow for 2 or 7 days but separated from it by a 0.4 μM polystyrene membrane. In 5 cases conditioned medium from patient cancer tissue was collected and ultracentrifuged, and microvesicles were collected for co-culture (3) and vesicle characterization (3). Explanted human marrow was harvested from cultures and RNA extracted. Real-time reverse transcriptase-polymerase chain reaction was done for select prostate specific genes. Marrow exposed to human prostate tumor or isolated microvesicles in culture in 4 and 3 cases, respectively, showed at least 2-fold or greater prostate gene expression than control marrow. In 1 case in which normal prostate was co-cultured there were no prostate gene increases in normal marrow. Prostate cancer tumor cells co-cultured with human bone marrow cells induce prostate specific gene expression. The proposed mechanism of transfer of genetic material is via microvesicles. This represents an opportunity for novel therapeutic agents, such as antibodies, to block microvesicle release from cancer cells or for agents that may block cells from accepting microvesicles.
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