动物实验 z-bo 2020-08-27 466

　　Scientists from Belgium have demonstrated for the first time how tumor cells of origin control the aggressiveness and metastatic properties of tumor cells.

　　"Tumor heterogeneity" refers to the difference between tumors in different patients and between different cells in the same tumor. The existence of this heterogeneity will affect the diagnosis, treatment and prognosis of cancer patients. In order to explain the heterogeneity of tumors, scientists have proposed different mechanisms, such as epithelial mesenchymal transition (EMT), in which epithelial tumor cells lose their adhesion and gain the migration characteristics of mesenchymal cells. This process is related to tumor metastasis. Related to drug resistance. Why some tumors have EMT while others do not? The reason may reflect the difference in tumor cells of origin, but this possibility has not been studied so far.

　　This is the first proof that, for squamous cell carcinoma of the skin, cancer cells of origin control the EMT process. Related research results were published in the international academic journal Cell Stem Cell.

　　In this new study, researchers used genetically engineered mice to trace the lineage of cancer cells of origin and detect the expression of mutant genes in different parts of the epidermis that induce cancer. Surprisingly, tumors originating from hair follicles are usually mesenchymal tumors that undergo EMT process and are highly aggressive, while skin cancers originating from the epidermis of hair follicles are highly differentiated epithelial cancers. These data indicate that hair follicle stem cells and their offspring are prone to EMT process and metastasis, indicating that the cancer cells of origin are closely related to the aggressiveness of tumors.

　　In order to understand the mechanism, the researchers studied the differences in the transcription and epigenetic profiles of cancer cells of different origins and corresponding tumors. They found that the epigenetics and transcriptional profiles of cancer cells of origin can affect the transformation of oncogene target cells to the highly differentiated or more aggressive direction of the epithelium, indicating that cancer cells of origin play an important role in this transition. The researchers said that the genes involved in EMT are already activated in the originating cancer cells, which will promote the EMT process of cancer cells.

　　The author of the article pointed out: “Combining genome-wide transcriptional profiling and epigenetic profiling, we can now determine which genes can bind to specific DNA regions and regulate tumor cell gene expression. The discovery of these gene networks that regulate different tumor functions can help design blockades. New strategies to interrupt tumorigenesis and EMT processes help improve tumor response to treatment and reduce metastasis."