Mansour Hager, Hassan Ghmkin, Afify Said M, Yan Ting, Seno Akimasa, Seno Masaharu
Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan.
Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, Japan.
Methods Protoc. 2020 Aug 21;3(3):60. doi: 10.3390/mps3030060.
Metastasis includes the dissemination of cancer cells from a malignant tumor and seed in distant sites inside the body forming secondary tumors. Metastatic cells from the primary tumor can move even before the cancer is detected. Therefore, metastases are responsible for more than 90% of cancer-related deaths. Over recent decades there has been adequate evidence suggesting the existence of CSCs with self-renewing and drug-resistant potency within heterogeneous tumors. Cancer stem cells (CSCs) act as a tumor initiating cells and have roles in tumor retrieve and metastasis. Our group recently developed a unique CSC model from mouse induced pluripotent stem cells cultured in the presence of cancer cell-conditioned medium that mimics tumors microenvironment. Using this model, we demonstrated a new method for studying metastasis by intraperitoneal transplantation of tumors and investigate the metastasis ability of cells from these segments. First of all, CSCs were injected subcutaneously in nude mice. The developed malignant tumors were minimized then transplanted into the peritoneal cavity. Following this, the developed tumor in addition to lung, pancreas and liver were then excised and analyzed. Our method showed the metastatic potential of CSCs with the ability of disseminated and moving to blood circulation and seeding in distant organs such as lung and pancreas. This method could provide a good model to study the mechanisms of metastasis according to CSC theory.
转移包括癌细胞从恶性肿瘤扩散并在体内远处部位着床形成继发性肿瘤。原发性肿瘤的转移细胞甚至在癌症被检测到之前就可以移动。因此，转移导致了超过90%的癌症相关死亡。近几十年来，有充分的证据表明在异质性肿瘤中存在具有自我更新和耐药能力的癌症干细胞（CSCs）。癌症干细胞作为肿瘤起始细胞，在肿瘤复发和转移中发挥作用。我们的团队最近从在癌细胞条件培养基存在下培养的小鼠诱导多能干细胞中开发出了一种独特的CSC模型，该培养基模拟肿瘤微环境。利用这个模型，我们展示了一种通过肿瘤腹腔内移植来研究转移的新方法，并研究了这些片段中细胞的转移能力。首先，将CSCs皮下注射到裸鼠体内。然后将形成的恶性肿瘤缩小并移植到腹腔中。在此之后，除了肺、胰腺和肝脏之外，将形成的肿瘤切除并进行分析。我们的方法显示了CSCs具有转移潜力，能够扩散并进入血液循环，并在肺和胰腺等远处器官着床。这种方法可以根据CSC理论为研究转移机制提供一个良好的模型。
