PO.TB04.08 · 肿瘤生物学
利用体内生物发光成像建立体内转移性前列腺肿瘤模型并随访进展
In vivo metastatic prostate tumor model development and follow-up progression using in vivo bioluminescence imaging
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
前列腺癌是男性中最常被诊断的恶性肿瘤，也是继肺癌之后位居第二的癌症相关死亡原因。其发病率在高收入地区最高。尽管广泛的筛查使约80%的病例得以在仍局限于器官内时被检出，但仍有15-20%的患者在就诊时已存在局部区域或远处转移。在美国，被诊断为转移性疾病的男性比例近年来持续上升，尤其在较年轻的患者中更为明显。临床结局与诊断时的肿瘤分级和分期密切相关；与局限性肿瘤患者相比，转移性疾病患者的总生存期显著缩短。主要转移部位为淋巴结和骨骼，其次为肝脏和肺。然而，很少有临床前模型能够有效重现这些晚期阶段，这为评估新型治疗药物造成了关键的空白。
在此，我们描述了通过胫骨内或动脉内注射22Rv1-Luc-mCherry前列腺癌细胞，在免疫缺陷雄性小鼠中建立肝转移和肺转移的方法。每周监测小鼠临床状况和体重三次。在五周内每周一次通过体内生物发光成像评估肿瘤进展。安乐死时，采集主要器官进行离体成像，以确认转移定位。
胫骨内接种后，生物发光在最初两周首先在注射部位增强，随后在第15天至第42天主要出现在肝脏和肺部。离体成像证实了这些发现。动脉内接种后，早期生物发光主要在骨骼中检出直至第28天，随后在第28天至第35天间肝脏内生物发光明显增强。离体成像证实转移播散至肝脏、肢体骨骼、脊柱和精囊。
总之，我们报道了一种可重复的转移性前列腺癌模型，该模型模拟了晚期疾病的关键特征，为新型治疗化合物的临床前评估提供了有价值的平台
查看英文原文 English abstract
Prostate cancer is the most frequently diagnosed malignancy in men and the second leading cause of cancer-related death after lung cancer. Its incidence is highest in high-income regions. Although widespread screening allows approximately 80% of cases to be detected while still organ-confined, 15-20% of patients present with locoregional or distant metastases. In the United States, the proportion of men diagnosed with metastatic disease has been rising in recent years, particularly among younger patients. Clinical outcome strongly correlates with tumor grade and stage at diagnosis; men with metastatic disease have significantly reduced overall survival compared with those with localized tumors. The primary metastatic sites are lymph nodes and bone, followed by liver and lung. However, few preclinical models effectively recapitulate these advanced stages, creating a critical gap for evaluating novel therapeutics.
Here, we describe the establishment of liver and lung metastases in immunodeficient male mice using 22Rv1-Luc-mCherry prostate cancer cells delivered via intratibial or intra-arterial injection. Mice were monitored three times per week for clinical condition and body weight. Tumor progression was assessed by in vivo bioluminescence imaging once per week for five weeks. At euthanasia, major organs were collected for ex vivo imaging to confirm metastatic localization.
Following intratibial inoculation, bioluminescence increased initially at the injection site during the first two weeks, then predominantly in the liver and lungs from days 15 to 42. These findings were confirmed by ex vivo imaging. After intra-arterial inoculation, early bioluminescence was detected primarily in bone through day 28, followed by a marked increase in the liver between days 28 and 35. Ex vivo imaging verified metastatic dissemination to the liver, limb bones, spinal column, and seminal vesicles.
In summary, we report a reproducible metastatic prostate cancer model that mimics key features of late-stage disease, providing a valuable platform for preclinical evaluation of new therapeutic compounds
利益披露 Disclosure
V. Faugeroux, None..
N. Hoffmann, None..
S. Belderbos, None..
M. Albanese, None..
K. Herry, None..
N. Ancellin, None..
C. Mignard, None..
M. Hilairet de Boisferon, None.