Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
Program in Cancer Biology, Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
Clin Exp Metastasis. 2020 Apr;37(2):247-255. doi: 10.1007/s10585-020-10025-3. Epub 2020 Feb 12.
Current laboratory models of lymphatic metastasis generally require either genetically modified animals or are technically challenging. Herein, we have developed a robust protocol for the induction of intralymphatic metastasis in wild-type mice with reproducible outcomes. To determine an optimal injection quantity and timeline for tumorigenesis, C57Bl/6 mice were injected directly into the mesenteric lymph duct (MLD) with varying numbers of syngeneic murine colon cancer cells (MC38) or gastric cancer cells (YTN16) expressing GFP/luciferase and monitored over 2-4 weeks. Tumor growth was tracked via whole-animal in vivo bioluminescence imaging (IVIS). Our data indicate that the injection of tumor cells into the MLD is a viable model for lymphatic metastasis as necropsies revealed large tumor burdens and metastasis in regional lymph nodes. This protocol enables a closer study of the role of lymphatics in cancer metastasis and opens a window for the development of novel approaches for treatment of metastatic diseases.
目前，淋巴转移的实验室模型通常需要经过基因改造的动物，或者技术上具有挑战性。在此，我们开发了一种稳健的方案，可在野生型小鼠中诱导淋巴内转移，结果具有可重复性。为了确定肿瘤发生的最佳注射数量和时间，我们将不同数量的表达 GFP/荧光素酶的同源鼠结肠癌细胞 (MC38) 或胃癌细胞 (YTN16) 直接注射到肠系膜淋巴管 (MLD) 中，并在 2-4 周内进行监测。通过小动物活体生物发光成像 (IVIS) 跟踪肿瘤生长情况。我们的数据表明，将肿瘤细胞注射到 MLD 中是一种可行的淋巴转移模型，因为尸检显示有大量肿瘤负荷和区域淋巴结转移。该方案使人们能够更深入地研究淋巴管在癌症转移中的作用，并为治疗转移性疾病开辟了新的方法。
