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article · Bioengineering

Metastasis of Cancer Stem Cells Developed in the Microenvironment of Hepatocellular Carcinoma

201931 citationsOpen accessKafr el-Sheikh University

In plain language

Cancer metastasis occurs when malignant cells spread from their initial site to distant tissues, presenting a major barrier to effective cancer treatment. In this investigation, mouse induced pluripotent stem cells were converted into cancer stem cells by culturing them in conditioned medium from the Huh7 hepatocellular carcinoma cell line. When transplanted into the liver or spleen of nude mice, these converted cells generated malignant tumours accompanied by metastatic lesions in the lungs and liver, in contrast to unconverted stem cells which formed benign teratomas. Cells isolated from the primary tumours and metastatic nodules maintained stemness markers, including Nanog, Klf4, and c-Myc, while acquiring cancer stem markers such as CD90, CD44, and ALDH1. Furthermore, metastatic markers including Slug, Twist1, and vimentin were expressed at higher levels in primary tumour cells than in metastatic nodules.

Key takeaways

  • Mouse induced pluripotent stem cells exposed to hepatocellular carcinoma conditioned medium successfully converted into metastatic cancer stem cells.
  • The converted cells generated malignant tumours with liver and lung metastases in nude mice, unlike unconverted stem cells which developed teratomas.
  • Cultured cells from both primary tumours and metastatic nodules retained pluripotency markers while acquiring cancer stem cell markers.
  • Metastatic markers were expressed at higher levels in the primary tumour cells than in the metastatic nodules.

Why it matters

Metastasis remains the principal cause of cancer treatment failure. Establishing reliable experimental models that accurately replicate how tumours develop and spread is critical for understanding malignancy. By showing that non-cancerous stem cells can be directed to model metastatic behaviour, this approach offers a controlled platform for investigating how cancer stem cells establish secondary tumours in distant organs.

Commercialisation angle

This work provides an animal model for academic and biomedical researchers investigating tumour metastasis and cancer stem cell biology. The primary application is as an experimental research tool to study metastatic mechanisms, which could inform future drug discovery. Because the findings represent early-stage laboratory research in mouse models, direct commercial applications such as standard screening platforms or clinical therapeutics remain distant.

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Abstract

Metastasis develops when cancer cells spread from the primary site of a malignant tumor to the surrounding and distant tissues, and it is the most critical problem in cancer treatment. Our group developed cancer stem cells (CSCs) from induced pluripotent stem cells (iPSCs) in the presence of a conditioned medium (CM) of cancer-derived cells. The CSCs were characterized by the formation of malignant tumors in vivo, followed by metastasis. In this study, CSCs converted from mouse iPSCs in the presence of CM from hepatocellular carcinoma (HCC) cell line Huh7 cells. These converted cells (miPS-Huh7cm cells) were established as the metastatic cells. The generated CSCs were injected into the liver or spleen of nude mice. Almost one month after transplantation, the tumors were excised, and the primary cultured cells derived from the malignant tumors and metastatic nodules were evaluated by stemness and metastatic markers to compare their differences. The miPS-Huh7cm cells exhibited metastatic potential, and efficiently formed malignant tumors with lung and/or liver lesions in vivo, whereas the injected miPS formed teratoma. The primary cultured cells derived from the malignant tumors and metastatic nodules sustained the expression of stemness markers, such as Nanog, Klf4 and c-Myc, and acquired cancer stem markers, such as CD90, CD44 and ALDH1. Simultaneously, the expression of metastatic markers, such as Slug, Twist1 and vimentin, in primary cells derived from the malignant tumors, was higher than in metastatic nodules. The CSCs derived from iPSCs, forming malignant tumors and displaying high metastasis, will provide a good animal model to study the mechanisms of metastasis.

Research topics

  • Cancer Cells and Metastasis
  • Pluripotent Stem Cells Research
  • Tissue Engineering and Regenerative Medicine

Sustainable Development Goals

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DOI: 10.3390/bioengineering6030073

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