Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada.
The Department of Medical Biophysics, The University of Western Ontario, London, Ontario, Canada.
Sci Rep. 2018 Jun 12;8(1):8930. doi: 10.1038/s41598-018-27208-4.
The mechanisms that influence metastatic growth rates are poorly understood. One mechanism of interest known as concomitant tumour resistance (CTR) can be defined as the inhibition of metastasis by existing tumour mass. Conversely, the presence of a primary tumour has also been shown to increase metastatic outgrowth, termed concomitant tumour enhancement (CTE). The majority of studies evaluating CTR/CTE in preclinical models have relied on endpoint histological evaluation of tumour burden. The goal of this research was to use conventional magnetic resonance imaging (MRI), cellular MRI, and bioluminescence imaging to study the impact of a primary tumour on the development of brain metastases in a syngeneic mouse model. Here, we report that the presence of a 4T1 primary tumour significantly enhances total brain tumour burden in Balb/C mice. Using in vivo BLI/MRI we could determine this was not related to differences in initial arrest or clearance of viable cells in the brain, which suggests that the presence of a primary tumour can increase the proliferative growth of brain metastases in this model. The continued application of our longitudinal cellular and molecular imaging tools will yield a better understanding of the mechanism(s) by which this physiological inhibition (CTR) and/or enhancement (CTE) occurs.
目前人们对影响转移生长速度的机制还知之甚少。有一种名为伴随肿瘤抵抗(concomitant tumour resistance,CTR)的机制引起了人们的关注,它可以定义为现有肿瘤质量对转移的抑制作用。相反,原发肿瘤的存在也被证明会增加转移生长,称为伴随肿瘤促进(concomitant tumour enhancement,CTE)。大多数评估临床前模型中 CTR/CTE 的研究都依赖于肿瘤负荷的终点组织学评估。本研究的目的是使用常规磁共振成像(magnetic resonance imaging,MRI)、细胞 MRI 和生物发光成像来研究原发肿瘤对同源小鼠模型中脑转移发展的影响。在这里,我们报告说,存在 4T1 原发肿瘤会显著增加 Balb/C 小鼠的总脑肿瘤负担。通过体内生物发光成像/MRI,我们可以确定这与在大脑中最初的存活细胞的滞留或清除差异无关,这表明在该模型中,原发肿瘤的存在可以增加脑转移的增殖生长。持续应用我们的纵向细胞和分子成像工具将更好地理解这种生理抑制(CTR)和/或增强(CTE)发生的机制。
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