Hyaluronidase expression induces prostate tumor metastasis in an orthotopic mouse model
Hyaluronidase expression induces prostate tumor metastasis in an orthotopic mouse model
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DOI：
10.2353/ajpath.2006.060324
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发表时间：
2006-10-01
影响因子：
6
通讯作者：
Simpson, Melanie A.
中科院分区：
文献类型：
--
作者：
Kovar, Joy L.;Johnson, Mark A.;Simpson, Melanie A.
前列腺癌进展的分子机制经常通过原位注射侵袭性细胞系在小鼠中进行研究，其产生自发转移到淋巴结的原发性肿瘤。在这份报告中，我们的特点是人前列腺癌细胞系22 Rv 1在原位系统和评估透明质酸酶Hyal 1，浸润性人前列腺癌的相关性，在这个模型中的进展的功能相关性。为了提供对这些过程的实时洞察，我们首先验证了使用表皮生长因子缀合的荧光团来照亮原位前列腺肿瘤及其在整个动物成像中的转移。接受前列腺内注射的动物在整个6周期间进行跟踪。肿瘤大小与22例前列腺肿瘤的总荧光强度相关性为92%。与高度致瘤性和转移性的PC 3 M-LN 4细胞相反，22 Rv 1系是原位致瘤性的，但不转移，尽管肿瘤尺寸较大。在具有PC 3 M-LN 4肿瘤的动物中，在终点解剖时成功地对淋巴结转移成像。用Hyal 1稳定转染22 Rv 1细胞并不改变原发性原位肿瘤的生长动力学，但所有植入Hyal 1转染子的动物均表现出肿瘤阳性的主动脉旁淋巴结。Hyal 1被认为是前列腺癌转移进展的诱导物。
Molecular mechanisms of prostate cancer progression are frequently studied in mice by orthotopic injection of aggressive cell lines, which yield primary tumors that spontaneously metastasize to lymph nodes. In this report, we characterized the human prostate carcinoma cell line 22Rv1 in an orthotopic system and evaluated the functional relevance of the hyaluronidase Hyal1, a correlate of invasive human prostate cancer, to progression in this model. To provide real-time insights into these processes, we first validated use of an epidermal growth factor-conjugated fluorophore to illuminate orthotopic prostate tumors and their metastases in whole animal imaging. Animals receiving intraprostatic injections were tracked throughout a 6-week period. Tumor sizes were correlated 92% with total fluorescence intensities of 22 prostate tumors. In contrast to the highly tumorigenic and metastatic PC3M-LN4 cells, the 22Rv1 line was orthotopically tumorigenic but not metastatic, despite larger tumor sizes. Lymph node metastasis was successfully imaged in animals with PC3M-LN4 tumors on endpoint dissection. Stable transfection of 22Rv1 cells with Hyal1 did not alter growth kinetics of primary orthotopic tumors, but all animals implanted with Hyal1 transfectants exhibited tumor-positive para-aortic lymph nodes. Hyal1 is implicated as an inducer of prostate cancer metastatic progression.