Animal experiment: NATCOMMUN|Zebrafish tumor transplantation model reveals the metastasis and differentiation characteristics of melanoma

  The main feature of cancer is the uncontrolled growth of cells, but if this uncontrolled growth is only a problem of cancer cells, then the cancer patient can usually be treated easily with surgery. However, what makes cancer so dangerous is that cancer cells invade other tissues of the body, that is, move to other normal areas of the body. Of course, metastatic melanoma is also very malignant and difficult to treat. Through the detection and analysis of melanoma samples, the researchers found that certain cells only showed certain proliferation characteristics at first, while other cells were aggressive and migratory. Now, the researchers say, the constant switching between these behaviors, in other words, allows cells to form new tumors in the same area. These cells are also aggressive and can invade other parts of the body. It is easy to spread on the parts.

  Currently, researchers do not know why this is happening. In this study, the researchers hope to clarify the molecular mechanisms by which these melanoma cells change various behaviors. Transgenic zebrafish are a combination of specific melanoma cell lines and gene knockout clear zebrafish. This study revealed the differentiation of melanoma cells between translocation and spread. The researchers first created a transgenic zebrafish strain using the human BRAF V600E gene, which is driven by the melanosome-specific mitfa promoter and the green fluorescent protein (GFP) reporter gene, and then used the zebrafish strain. The zebrafish specificity was obtained with the melanoma cell line-ZMEL1GFP, which can be transplanted into transparent fish and visualized by in vivo imaging (below). ZMEL1GFP cancer cells were transplanted subcutaneously (Figure 1a, top). This is similar to human cancer metastasis. The local tumor was originally mitf-GFP +, but it was completely colorless. After an incubation period of 7-14 days, 100% of locally transplanted skin tumors showed pigmentation and melanocyte differentiation. At the same time, secondary subcutaneous metastases were not initially stained with mitf-GFP+, but metastasis appeared after 14 days, with 53% staining (Figure 1a). This indicates that the metastasis was undifferentiated at the beginning, but has differentiated after the metastasis.