PDF(Pubmed)
Abstract：
UNASSIGNED: Resection of colorectal liver metastasis is the standard of care for patients with Stage IV CRC. Despite undoubtedly improving the overall survival of patients, pHx for colorectal liver metastasis frequently leads to disease recurrence. The contribution of this procedure to metastatic colorectal cancer at a molecular level is poorly understood. We designed a mouse model of orthograde metastatic colorectal cancer (CRC) to investigate the effect of partial hepatectomy (pHx) on tumor progression.
UNASSIGNED: CRC organoids were implanted into the cecal walls of wild type mice, and animals were screened for liver metastasis. At the time of metastasis, 1/3 partial hepatectomy was performed and the tumor burden was assessed longitudinally using MRI. After euthanasia, different tissues were analyzed for immunological and transcriptional changes using FACS, qPCR, RNA sequencing, and immunohistochemistry.
UNASSIGNED: Mice that underwent pHx presented significant liver hypertrophy and an increased overall metastatic load compared with SHAM operated mice in MRI. Elevation in the metastatic volume was defined by an increase in de novo liver metastasis without any effect on the growth of each metastasis. Concordantly, the livers of pHx mice were characterized by neutrophil and bacterial infiltration, inflammatory response, extracellular remodeling, and an increased abundance of tight junctions, resulting in the formation of a premetastatic niche, thus facilitating metastatic seeding.
UNASSIGNED: Regenerative pathways following pHx accelerate colorectal metastasis to the liver by priming a premetastatic niche.
UNASSIGNED: CRC organoids were implanted into the cecal walls of wild type mice, and animals were screened for liver metastasis. At the time of metastasis, 1/3 partial hepatectomy was performed and the tumor burden was assessed longitudinally using MRI. After euthanasia, different tissues were analyzed for immunological and transcriptional changes using FACS, qPCR, RNA sequencing, and immunohistochemistry.
UNASSIGNED: Mice that underwent pHx presented significant liver hypertrophy and an increased overall metastatic load compared with SHAM operated mice in MRI. Elevation in the metastatic volume was defined by an increase in de novo liver metastasis without any effect on the growth of each metastasis. Concordantly, the livers of pHx mice were characterized by neutrophil and bacterial infiltration, inflammatory response, extracellular remodeling, and an increased abundance of tight junctions, resulting in the formation of a premetastatic niche, thus facilitating metastatic seeding.
UNASSIGNED: Regenerative pathways following pHx accelerate colorectal metastasis to the liver by priming a premetastatic niche.
摘要：
■结直肠肝转移切除术是IV期CRC患者的标准护理。尽管无疑改善了患者的总体生存率，pHx用于结直肠肝转移经常导致疾病复发。该程序在分子水平上对转移性结直肠癌的贡献知之甚少。我们设计了一种正行转移性结直肠癌（CRC）的小鼠模型，以研究部分肝切除术（pHx）对肿瘤进展的影响。
■将CRC类器官植入野生型小鼠的盲肠壁，并对动物进行肝转移筛查。在转移的时候，进行1/3部分肝切除术，并使用MRI纵向评估肿瘤负荷。安乐死后,使用FACS分析不同组织的免疫学和转录变化，qPCR,RNA测序，和免疫组织化学。
■在MRI中，与SHAM手术小鼠相比，接受pHx的小鼠表现出明显的肝肥大和总体转移负荷增加。转移体积的升高由从头肝转移的增加定义，对每个转移的生长没有任何影响。和谐地，pHx小鼠的肝脏以中性粒细胞和细菌浸润为特征，炎症反应，细胞外重塑，和更多的紧密连接，导致了转移前生态位的形成，从而促进转移性播种。
■pHx后的再生途径通过启动转移前的生态位来加速结直肠向肝脏的转移。
■将CRC类器官植入野生型小鼠的盲肠壁，并对动物进行肝转移筛查。在转移的时候，进行1/3部分肝切除术，并使用MRI纵向评估肿瘤负荷。安乐死后,使用FACS分析不同组织的免疫学和转录变化，qPCR,RNA测序，和免疫组织化学。
■在MRI中，与SHAM手术小鼠相比，接受pHx的小鼠表现出明显的肝肥大和总体转移负荷增加。转移体积的升高由从头肝转移的增加定义，对每个转移的生长没有任何影响。和谐地，pHx小鼠的肝脏以中性粒细胞和细菌浸润为特征，炎症反应，细胞外重塑，和更多的紧密连接，导致了转移前生态位的形成，从而促进转移性播种。
■pHx后的再生途径通过启动转移前的生态位来加速结直肠向肝脏的转移。
