Use of FVB Myc-CaP cells as an immune competent, androgen receptor positive, mouse model of prostate cancer bone metastasis.

Use of FVB Myc-CaP cells as an immune competent, androgen receptor positive, mouse model of prostate cancer bone metastasis.
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DOI:
10.1016/j.jbo.2021.100386
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发表时间:
2021-10
影响因子:
3.4
通讯作者:
Cackowski FC
Cackowski FC
中科院分区:
医学2区
文献类型:
--
作者:
Wang Y;Herroon MK;Zielske SP;Ellis L;Podgorski I;Taichman RS;Cackowski FC

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小鼠前列腺癌 Myc-CaP 细胞很容易在 FVB/NJ 小鼠中形成骨肿瘤。骨内注射后肿瘤大体局限于骨内。 Myc-CaP 骨肿瘤具有混合的溶骨/骨硬化形态。同基因 Myc-CaP 肿瘤模拟前列腺癌骨转移的关键方面。前列腺癌(PCa)转移研究因缺乏与大多数患者中存在的疾病非常相似的动物模型而受到阻碍,这些动物模型转移至骨骼,依赖于雄激素受体(AR),并在免疫能力强的宿主中生长。在这里,我们调整 Myc-CaP 细胞系用作 PCa 雄激素依赖性、免疫能力骨转移模型并表征转移。将这些细胞注射到同基因 FVB/NJ 小鼠的左心室后,在大多数动物中形成骨转移;在 H&E 切片上很容易看到,并通过 Ar 和上皮细胞粘附分子的免疫组织化学证实。还观察到纵隔肿瘤。我们还用 tdTomato 标记 Myc-CaP 细胞,并通过流式细胞术证实骨中癌细胞的存在。为了使模型适应以骨为主的转移模式并进一步检查骨表型,我们用荧光素酶标记细胞,注射到胫骨中,并观察到仅在具有混合溶骨/成骨细胞表型的胫骨中形成肿瘤。与假注射对照相比,Myc-CaP 肿瘤的存在显着增加了胫骨骨体积。与假手术动物相比,带有胫骨肿瘤的动物的血浆中破骨细胞标记物TRAcP-5b没有显着变化。然而,来自 Myc-CaP 细胞的条件培养基在体外刺激了 FVB/NJ 小鼠骨髓中的破骨细胞形成。总体而言,注射到同系小鼠左心室或胫骨中的 Myc-CaP 细胞重现了人类转移性 PCa 的关键方面。
Mouse prostate cancer Myc-CaP cells readily form bone tumors in FVB/NJ mice. Tumors are grossly confined to bone after intraosseous injection. Myc-CaP bone tumors have a mixed osteolytic/osteosclerotic morphology. Syngeneic Myc-CaP tumors model key aspects of prostate cancer bone metastases. Prostate cancer (PCa) metastasis research has been hamstrung by lack of animal models that closely resemble the disease present in most patients – that metastasize to bone, are dependent on the androgen receptor (AR), and grow in an immune competent host. Here, we adapt the Myc-CaP cell line for use as a PCa androgen dependent, immune competent bone metastases model and characterize the metastases. After injection into the left cardiac ventricle of syngeneic FVB/NJ mice, these cells formed bone metastases in the majority of animals; easily visible on H&E sections and confirmed by immunohistochemistry for Ar and epithelial cell adhesion molecule. Mediastinal tumors were also observed. We also labeled Myc-CaP cells with tdTomato, and confirmed the presence of cancer cells in bone by flow cytometry. To adapt the model to a bone predominant metastasis pattern and further examine the bone phenotype, we labeled the cells with luciferase, injected in the tibia and observed tumor formation only in tibia with a mixed osteolytic/osteoblastic phenotype. The presence of Myc-CaP tumors significantly increased tibia bone volume as compared to sham injected controls. The osteoclast marker, TRAcP-5b was not significantly changed in plasma from tibial tumor bearing animals vs. sham animals. However, conditioned media from Myc-CaP cells stimulated osteoclast formation in vitro from FVB/NJ mouse bone marrow. Overall, Myc-CaP cells injected in the left ventricle or tibia of syngeneic mice recapitulate key aspects of human metastatic PCa.
DOI: 10.1177/1758835920967241
发表时间: 2020
影响因子: 4.9
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通讯作者: Roodman, G. David
DOI: 10.1002/jcb.25768
发表时间: 2017-04
影响因子: 4
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DOI: 10.1002/pros.23206
发表时间: 2016-09
期刊: The Prostate
影响因子: --
作者:
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