Department of Biology, University of North Carolina at Charlotte, 9201 University City Blvd, Charlotte, North Carolina, USA.
Infect Agent Cancer. 2012 May 29;7(1):11. doi: 10.1186/1750-9378-7-11.
Controversy exists as to the ability of human gammaherpesviruses to cause or exacerbate breast cancer disease in patients. The difficulty in conducting definitive human studies can be overcome by investigating developing breast cancer in a mouse model. In this study, we utilized mice latently infected with murine gammaherpesvirus 68 (HV-68) to question whether such a viral burden could exacerbate metastatic breast cancer disease using a mouse mammary tumor model.
Mice latently infected with HV-68 had a similar primary tumor burden, but much greater metastatic disease, when compared to mock treated mice given the transplantable tumor, 4 T1. This was true for lung lesions, as well as secondary tumor masses. Increased expression of pan-cytokeratin and VEGF-A in tumors from HV-68 infected mice was consistent with increased metastatic disease in these animals. Surprisingly, no viral particles could be cultured from tumor tissues, and the presence of viral DNA or RNA transcripts could not be detected in primary or secondary tumor tissues.
Latent HV-68 infection had no significant effect on the size of primary 4 T1 mammary tumors, but exacerbated the number of metastatic lung lesions and secondary tumors when compared to mock treated mice. Increased expression of the tumor marker, pan-cytokeratin, and VEGF-A in tumors of mice harboring latent virus was consistent with an exacerbated metastatic disease. Mechanisms responsible for this exacerbation are indirect, since no virus could be detected in cancerous tissues.
人γ疱疹病毒是否有能力引发或加重乳腺癌患者的疾病，目前仍存在争议。由于难以进行明确的人类研究，可以通过在小鼠模型中研究乳腺癌的发展来克服这一难题。在这项研究中，我们利用潜伏感染鼠γ疱疹病毒 68（HV-68）的小鼠来质疑这种病毒载量是否会通过移植性乳腺癌模型加重转移性乳腺癌疾病。
与接受移植性肿瘤 4T1 的假处理小鼠相比，潜伏感染 HV-68 的小鼠具有相似的原发性肿瘤负担，但转移性疾病要严重得多。这对于肺部病变以及继发性肿瘤肿块也是如此。HV-68 感染小鼠肿瘤中 pan-cytokeratin 和 VEGF-A 的表达增加与这些动物中转移性疾病的增加一致。令人惊讶的是，无法从肿瘤组织中培养出病毒颗粒，也无法在原发性或继发性肿瘤组织中检测到病毒 DNA 或 RNA 转录本。
潜伏的 HV-68 感染对原发性 4T1 乳腺肿瘤的大小没有显著影响，但与假处理小鼠相比，会加剧肺部转移病变和继发性肿瘤的数量。在携带潜伏病毒的小鼠肿瘤中，肿瘤标志物 pan-cytokeratin 和 VEGF-A 的表达增加与转移性疾病的加重一致。导致这种加重的机制是间接的，因为在癌组织中无法检测到病毒。
