[Animal modeling] - Animal model of hematogenous tumor metastasis

  Hematological metastasis can be seen in many organs, but the most common is in the lungs, followed by the liver and spleen. After invading blood vessels, tumor cells can reach distant organs with blood flow and continue to grow, forming metastatic tumors. The arterial wall is thicker and the pressure inside the tube is higher, so tumor cells often enter the blood through small veins, and a few can also pass through lymphatic vessels. The operating pathway of hematogenous metastasis is the same as the process of thromboembolism, that is, tumor cells invading the pulmonary veins pass through the right heart to the lungs, forming metastatic tumors in the lungs, such as osteosarcoma and other lung metastases; Tumor cells invading the portal vein system first form intrahepatic metastases, such as liver metastases from stomach and colon cancer; Tumor cells invading the pulmonary veins can reach various organs throughout the body through the left heart and aortic blood flow, with common metastases to the brain, bones, kidneys, and adrenal glands. In addition, tumor cells invading the thoracic, lumbar, and pelvic veins can also enter the spinal venous plexus (Batson spinal venous system) through anastomotic branches. For example, prostate cancer can metastasize to the spine and then to the brain through this pathway, without the need for lung metastasis. In fact, only a small number of cancer cells can detach from the primary lesion and enter the bloodstream, while the number of cancer cells that can eventually grow and form metastatic lesions in the "target organ" is even rarer. After injecting radiolabeled tumor cells into animal blood vessels and entering the bloodstream for 24 hours, only 1% of tumor cells can survive. At each stage of tumor cell metastasis, they may be killed by the body's immune function, and less than 1 ‰ of them reach this site to produce secondary lesions. Several models of hematogenous metastasis have been established to mimic the different pathways of cancer cell invasion:

  (1) The transfer model established by the method of injecting blood into the tail vein mainly involves lung metastasis, which may be accompanied by metastasis to other organs in the later stage. The characteristics of this model are simple operation, fast metastasis, and slightly different metastasis rates depending on the malignancy and metastasis potential of tumor cells. However, overall, this model has a higher metastasis rate and is commonly used to screen for anti-tumor metastasis drugs. When vaccinating, first take tumor cells in the exponential growth phase and make a suspension, usually diluted to 1 × A cell concentration of 10000000/ml was taken and 0.1ml was injected into the experimental animal body from the tail vein. Different tumor strains and cell numbers can affect the metastasis rate of the model, but many human tumor cell lines can achieve a metastasis rate of over 50% after long-term observation in immunodeficient mice. Mouse 816 melanoma cells were inoculated into the tail vein of C57BL/6 mice, and 100% of them showed lung metastasis at 3 weeks. Due to the presence of melanin, it is easy to directly observe and count lung metastatic nodules. It is important to note that when establishing a model of hematogenous metastasis of tumor cells directly inoculated into the tail vein, the cells should be thoroughly mixed and injected slowly. The concentration should not be too high to avoid obstruction and animal death. Someone used VX2 cell suspension (5 × More than 1000000 cells were inoculated into the ear vein of New Zealand rabbits, and after 3 weeks, the lung metastasis rate reached 100%. Some animals may have metastasis in other parts, and the vaccination route of this model is similar to that of intravenous inoculation in mice.

  (2) The intrasplenic injection of hematogenous metastasis model is similar to the injection of tumor cells through the tail vein, which can produce lung metastasis