HCT116 colorectal and MCF7 brest cancer cell lines xenografted into zebrafish embryos gives insight into the importance of microenviroment in tumor growth and metastasis for a future use of the model in clinical research

Resumo

In the last decades, zebrafish has emerged as one of the best models to modeling different human diseases due to his genetic similarity (75% of orthologous genes) establishing a viable, fast and low cost platform to test different strategies with the objective of get a deeper insight the mechanisms of action that lays underneath the diseases. One of the most studied diseases nowadays is cancer, a heterogeneous disease that constitutes a big deal for the oncologists all over the world due to his no homogeneous behavior that corresponds with individual differences between patients. For this reason, zebrafish has been used in cancer research by means of the xenograft technique (injection of human cancer cells in embryos or adults of this model organism) since 2005 when Haldi et al. demonstrated in a publication that the injection of human cancer cells inside the yolk of the zebrafish embryo is reliable and they can proliferate. Since then, the number of publications in which people perform xenografts with human cancer cells lines, patient derived xenografts (PDX) or microenvironment components is always rising. The objective of this technique is simulate a human-like microenvironment inside a model organism in which the cancer cells from the patient could be able to proliferate, migrate and metastasize in different places for testing different chemotherapeutic drugs with the objective of treat that specific cancer with a more personalized approach spending less time, costs and efficiency than the ‘mouse avatars’. This technology could be implemented in the hospitals all over the world to help the oncologists to take a better decision based on more robust data. As long as the xenograft technique has been implemented in zebrafish, mentioned before, there has been improvements to this technique and the conditions surrounding it. Nevertheless, there are some bottle necks with the necessity of being addressed with the objective of getting a more robust and informative technique in order to establish it in a near future in the personalized medicine field. One of the disadvantages of the xenograft technique is the one related to the incubation temperature of the embryos, trying to get a balance between their normal developmental temperature and the proper temperature of the injected cells. On the other hand, a more accurate and faster software for image analysis would be needed to track and quantify the injected cells in a more efficient way. Finally, it would be important to recreate the microenvironment of the tumor inside of the embryo by co-injecting different tumor components like macrophages or fibroblasts to see how do they behave against some therapies and, in this way, get closer to the native state of the tumor in the human body.