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Absence of XMRV and Closely Related Viruses in Primary Prostate Cancer Tissues Used to Derive the XMRV-Infected Cell Line 22Rv1

机译:在派生XMRV感染的细胞系22Rv1的原发性前列腺癌组织中不存在XMRV和紧密相关的病毒

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摘要

The 22Rv1 cell line is widely used for prostate cancer research and other studies throughout the world. These cells were established from a human prostate tumor, CWR22, that was serially passaged in nude mice and selected for androgen independence. The 22Rv1 cells are known to produce high titers of xenotropic murine leukemia virus-related virus (XMRV). Recent studies suggested that XMRV was inadvertently created in the 1990's when two murine leukemia virus (MLV) genomes (pre-XMRV1 and pre-XMRV-2) recombined during passaging of the CWR22 tumor in mice. The conclusion that XMRV originated from mice and not the patient was based partly on the failure to detect XMRV in early CWR22 xenografts. While that deduction is certainly justified, we examined the possibility that a closely related virus could have been present in primary tumor tissue. Here we report that we have located the original prostate tumor tissue excised from patient CWR22 and have assayed the corresponding DNA by PCR and the tissue sections by fluorescence in situ hybridization for the presence of XMRV or a similar virus. The primary tumor tissues lacked mouse DNA as determined by PCR for intracisternal A type particle DNA, thus avoiding one of the limitations of studying xenografts. We show that neither XMRV nor a closely related virus was present in primary prostate tissue of patient CWR22. Our findings confirm and reinforce the conclusion that XMRV is a recombinant laboratory-generated mouse virus that is highly adapted for human prostate cancer cells.
机译:22Rv1细胞系在全世界广泛用于前列腺癌研究和其他研究。这些细胞是从人类前列腺肿瘤CWR22建立的,该肿瘤在裸鼠中连续传代并选择了雄激素依赖性。已知22Rv1细胞会产生高滴度的异种鼠白血病病毒相关病毒(XMRV)。最近的研究表明,XMRV是在1990年代无意中产生的,当时两个小鼠白血病病毒(MLV)基因组(XMRV1之前和XMRV-2之前)在小鼠CWR22肿瘤传代期间重组。 XMRV起源于小鼠而非患者的结论部分基于早期CWR22异种移植物中未能检测到XMRV。尽管这一推论当然是合理的,但我们研究了原发肿瘤组织中可能存在密切相关的病毒的可能性。在这里,我们报告说,我们已经找到了从患者CWR22切除的原始前列腺肿瘤组织,并通过PCR和荧​​光原位杂交检测了相应的DNA是否存在XMRV或类似病毒。原发性肿瘤组织缺乏小鼠DNA,如通过PCR测定的脑池内A型颗粒DNA,从而避免了研究异种移植的局限性之一。我们显示,患者CWR22的原发前列腺组织中既没有XMRV也没有密切相关的病毒。我们的发现证实并加强了XMRV是重组实验室产生的小鼠病毒的结论,该病毒高度适用于人前列腺癌细胞。

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