A novel patient-derived intra-femoral xenograft model of bone metastatic prostate cancer that recapitulates mixed osteolytic and osteoblastic lesions.
A novel patient-derived intra-femoral xenograft model of bone metastatic prostate cancer that recapitulates mixed osteolytic and osteoblastic lesions.
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一种新型患者来源的骨转移性前列腺癌股骨内异种移植模型，再现了混合的溶骨性和成骨性病变。
DOI：
10.1186/1479-5876-9-185
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发表时间：
2011-10-28
影响因子：
7.4
通讯作者：
Jamieson CA
中科院分区：
文献类型：
--
作者：
Raheem O;Kulidjian AA;Wu C;Jeong YB;Yamaguchi T;Smith KM;Goff D;Leu H;Morris SR;Cacalano NA;Masuda K;Jamieson CH;Kane CJ;Jamieson CA
前列腺癌在大多数晚期患者中转移到骨骼，导致痛苦的衰弱性骨折，脊柱压迫和快速衰退。此外，前列腺癌骨转移通常对包括雄激素剥夺、放疗和化疗在内的标准治疗产生抗药性。目前很少有模型能够阐明骨微环境与前列腺癌相互作用的机制。因此，开发新的患者衍生的原位模型至关重要。在这里，我们报告了PCSD1（前列腺癌圣地亚哥1号）的发展和特征，PCSD1是一种新的患者来源的前列腺骨转移癌股骨内异种移植模型，概括了混合溶骨和成骨病变。在半关节成形术中切除了一例前列腺癌股骨转移瘤，并将其移植到Rag2-/-中；γ -c -/-小鼠股骨头内或皮下注射。使用RT-PCR和免疫组织化学分析发生的异种移植肿瘤的前列腺癌生物标志物表达。使用微计算机断层扫描（microCT）测量成骨、溶骨和混合性病变的形成。直接从患者身上分离的PCSD1细胞在所有小鼠股骨内或皮下植入Rag2-/-后均形成肿瘤；γc - / -小鼠。异种移植肿瘤在RT-PCR和免疫组化分析中表达人前列腺特异性抗原（PSA）。PCSD1肿瘤还表达AR、NKX3.1、角蛋白8和18以及AMACR。组织学和显微ct分析显示，股骨内PCSD1异种移植肿瘤形成溶骨和成骨混合病变。PCSD1肿瘤已在小鼠体内作为异种移植物在股骨内或皮下连续传代，以及在培养中生长。利用RT-PCR和免疫组织化学生物标志物分析，将PCSD1异种移植肿瘤定性为晚期腔内上皮性前列腺癌，并伴有骨转移。PCSD1股骨内异种移植物形成混合成骨/溶骨病变，与患者的骨病变非常相似。PCSD1是一种新的原发性前列腺癌骨转移源异种移植模型，用于研究骨转移性疾病，并开发抑制前列腺癌骨生态位生长的新疗法。
Prostate cancer metastasizes to bone in the majority of patients with advanced disease leading to painfully debilitating fractures, spinal compression and rapid decline. In addition, prostate cancer bone metastases often become resistant to standard therapies including androgen deprivation, radiation and chemotherapy. There are currently few models to elucidate mechanisms of interaction between the bone microenvironment and prostate cancer. It is, thus, essential to develop new patient-derived, orthotopic models. Here we report the development and characterization of PCSD1 (Prostate Cancer San Diego 1), a novel patient-derived intra-femoral xenograft model of prostate bone metastatic cancer that recapitulates mixed osteolytic and osteoblastic lesions. A femoral bone metastasis of prostate cancer was removed during hemiarthroplasty and transplanted into Rag2-/-;γc-/- mice either intra-femorally or sub-cutaneously. Xenograft tumors that developed were analyzed for prostate cancer biomarker expression using RT-PCR and immunohistochemistry. Osteoblastic, osteolytic and mixed lesion formation was measured using micro-computed tomography (microCT). PCSD1 cells isolated directly from the patient formed tumors in all mice that were transplanted intra-femorally or sub-cutaneously into Rag2-/-;γc-/- mice. Xenograft tumors expressed human prostate specific antigen (PSA) in RT-PCR and immunohistochemical analyses. PCSD1 tumors also expressed AR, NKX3.1, Keratins 8 and 18, and AMACR. Histologic and microCT analyses revealed that intra-femoral PCSD1 xenograft tumors formed mixed osteolytic and osteoblastic lesions. PCSD1 tumors have been serially passaged in mice as xenografts intra-femorally or sub-cutaneously as well as grown in culture. PCSD1 xenografts tumors were characterized as advanced, luminal epithelial prostate cancer from a bone metastasis using RT-PCR and immunohistochemical biomarker analyses. PCSD1 intra-femoral xenografts formed mixed osteoblastic/osteolytic lesions that closely resembled the bone lesions in the patient. PCSD1 is a new primary prostate cancer bone metastasis-derived xenograft model to study metastatic disease in the bone and to develop novel therapies for inhibiting prostate cancer growth in the bone-niche.
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影响因子：
82.9
作者：
Chen, CD;Welsbie, DS;Sawyers, CL
通讯作者：
Sawyers, CL
DOI：
10.1126/science.1189992
发表时间：
2010-07-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Goldstein AS;Huang J;Guo C;Garraway IP;Witte ON
通讯作者：
Witte ON
影响因子：
2.8
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.
通讯作者：
Witte, Owen N.
影响因子：
2.8
作者：
Corey, E;Quinn, JE;Vessella, RL
通讯作者：
Vessella, RL
影响因子：
7
作者：
Kim, Jung H.;Dhanasekaran, Saravana M.;Chinnaiyan, Arul M.
通讯作者：
Chinnaiyan, Arul M.