Felton Jessica, Cheng Kunrong, Shang Aaron C, Hu Shien, Larabee Shannon M, Drachenberg Cinthia B, Raufman Jean-Pierre
Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
J Cancer Metastasis Treat. 2018;4. doi: 10.20517/2394-4722.2018.39. Epub 2018 Sep 27.
Strong evidence reveals important differences between cancers in the proximal . distal colon. Animal models of metastatic colon cancer are available but with varying degrees of reproducibility and several important limitations. We explored whether there were regional differences in the location of murine colon cancers and assessed the utility of murine models to explore the biological basis for such differences.
We re-analyzed data from our previous studies to assess the regional distribution of murine colon cancer. In survival surgery experiments, we injected HT-29 human colon cancer cells into the wall of the cecum or distal colon of Nu(NCr)-Foxn1 or NOD.Cg-PrkdcIl2rg/SzJ mice and compared the development of primary tumors and metastases.
Within 7-17 weeks after intramural cecal injection of HT-29 cells, eight mice failed to develop solid primary tumors or metastases. In contrast, within four weeks after cell injection into the distal colon, 13 mice developed metastases - 12 mice developed subcutaneous metastases; of these, four developed liver metastases and one developed both liver and lung metastases. One mouse developed liver metastases only. Histological examination confirmed these lesions were adenocarcinomas.
Our findings reveal the preferential growth of murine colon neoplasia and invasive human orthotopic xenografts in the distal mouse colon. The new approach of injecting cells into the distal colon wall results in a pattern of colon cancer development that closely mimics the progression of metastatic colon cancer in humans. This novel model of colon neoplasia has great potential for exploring anatomical differences in colon cancer and testing novel therapeutics.
有力证据显示近端和远端结肠癌存在重要差异。转移性结肠癌的动物模型虽有，但再现性各异且存在若干重要局限性。我们探究了小鼠结肠癌发生部位是否存在区域差异，并评估了小鼠模型在探索此类差异生物学基础方面的效用。
我们重新分析了之前研究的数据，以评估小鼠结肠癌的区域分布。在生存手术实验中，我们将HT - 29人结肠癌细胞注入Nu(NCr)-Foxn1或NOD.Cg-PrkdcIl2rg/SzJ小鼠的盲肠壁或远端结肠壁，并比较原发性肿瘤和转移灶的发生情况。
在盲肠壁内注射HT - 29细胞后的7 - 17周内，8只小鼠未形成实体原发性肿瘤或转移灶。相比之下，在将细胞注入远端结肠后的4周内，13只小鼠发生了转移——12只小鼠出现皮下转移；其中4只发生肝转移，1只同时发生肝和肺转移。1只小鼠仅发生肝转移。组织学检查证实这些病变为腺癌。
我们的研究结果揭示了小鼠结肠肿瘤和侵袭性人原位异种移植物在小鼠远端结肠的优先生长情况。将细胞注入远端结肠壁的新方法导致了一种结肠癌发展模式，该模式紧密模拟了人类转移性结肠癌的进展。这种新型结肠肿瘤模型在探索结肠癌的解剖学差异和测试新型疗法方面具有巨大潜力。
