PO.TB02.01 · 肿瘤生物学
从局部生长到远处转移:用于建模癌症进展的多功能体内成像平台
From local growth to distant metastasis: A versatile in vivo imaging platform for modeling cancer progression
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景:全面理解癌症进展需要能够动态捕获局部肿瘤生长和全身播散多步骤过程的实验模型。传统模型往往只重现这一级联过程中孤立的方面,从而限制了其转化相关性。
目的:建立并验证一个整合的体内平台,利用基于荧光素酶的成像来定量建模癌症进展的不同阶段——从原发移植到嗜器官性播散。
方法:我们在免疫缺陷小鼠中构建了一系列位点特异性癌症模型,通过生物发光成像(BLI)持续监测疾病进展。这些模型包括:1. 心内注射MDA-MB-231-Luc2细胞以建模播散性转移性种植。2. 胫骨内和颅内接种以评估乳腺癌细胞在骨和脑微环境中的位点特异性生长。3. 静脉注射Ba/F3和淋巴瘤细胞以模拟血行播散。4. 对颅内移植拓扑结构的系统分析,其中将A375-GFP-Luc细胞接种于立体定位坐标——前囟(bregma)前方0.5 mm、前方1.5 mm和后方0.5 mm处。
结果:该平台稳健地重现了多种疾病表型。心内注射导致广泛的生物发光信号,提示转移性定植。原位胫骨和颅内接种导致进行性、可量化的局部肿瘤生长。静脉注射造血细胞产生了白血病增殖的全身模式。重要的是,颅内植入部位成为疾病进展的关键决定因素:与前部位点相比,前囟后方的注射与显著更高的转移性播散倾向相关。
结论:我们提出了一个经过验证且多功能的体内平台,能够在多种疾病背景下对肿瘤动态进行时空定量。这一整合系统为研究器官特异性肿瘤生物学以及评估针对原发和转移性疾病的治疗疗效提供了强大工具。
查看英文原文 English abstract
Background: A comprehensive understanding of cancer progression requires experimental models capable of dynamically capturing both localized tumor growth and the multi-step process of systemic dissemination. Conventional models often recapitulate isolated aspects of this cascade, thereby limiting their translational relevance.
Objective: To establish and validate an integrated in vivo platform that utilizes luciferase-based imaging to quantitatively model distinct stages of cancer progression-from primary engraftment to organotropic dissemination.
Methods: We engineered a series of site-specific cancer models in immunodeficient mice, with disease progression continuously monitored by bioluminescent imaging (BLI). These included: 1. Intracardiac injection of MDA-MB-231-Luc2 cells to model disseminated metastatic seeding. 2. Intratibial and intracranial inoculation to evaluate site-specific growth of breast cancer cells in bone and brain microenvironments. 3. Intravenous injection of Ba/F3 and lymphoma cells to simulate hematogenous dissemination. 4. A systematic analysis of intracranial engraftment topography, where A375-GFP-Luc cells were inoculated at stereotactic coordinates 0.5 mm anterior, 1.5 mm anterior, and 0.5 mm posterior to the bregma.
Results: The platform robustly recapitulated diverse disease phenotypes. Intracardiac injection resulted in widespread bioluminescent signals indicative of metastatic colonization. Orthotopic tibial and intracranial inoculations led to progressive, quantifiable local tumor growth. Intravenous injection of hematopoietic cells produced a systemic pattern of leukemic proliferation. Importantly, the intracranial implantation site emerged as a key determinant of disease progression: injections posterior to the bregma were associated with a significantly greater propensity for metastatic dissemination compared to anterior sites.
Conclusion: We present a validated and versatile in vivo platform that enables the spatiotemporal quantification of tumor dynamics across multiple disease contexts. This integrated system provides a powerful tool for investigating organ-specific tumor biology and evaluating therapeutic efficacy against both primary and metastatic disease.
利益披露 Disclosure
N. Li,
Kyinno Biotechnology Co., LTD Employment.
H. Huang,
Kyinno Biotechnology Co., LTD Employment.
X. Zhong,
Kyinno Biotechnology Co., LTD Employment.
X. Duan,
Kyinno Biotechnology Co., LTD Employment.
X. Lan,
Kyinno Biotechnology Co., LTD Employment.
J. Ning,
Kyinno Biotechnology Co., LTD Employment.
F. Hao,
Kyinno Biotechnology Co., LTD Employment.