There are many systems involved with metastasis in cancer. One of many is the EMT system. This system is the epithelial-mesenchymal transitions, which is a process when epithelial cells acquire mesenchymal properties. This means fibroblast properties and an increase in motility. Cancerous cells enter the blood stream during this transition phase and metastasis occurs. The process of the EMT system is that first cancer cells from the primary tumor invade the local tissue and invade nearby microvessels by entering the circulation. After, tumor cells are trapped in the microvessels of distant tissues, where they leave the bloodstream by extravasation. The final step is the acquired ability of micrometastic deposits to form macroscopic metastes, which is colonization.
Another system is the process of angiogenesis. This is the process of creating new blood vessels. This process involves the migration, growth, and differentiation of endothelial cells. This stands for bone marrow cells. It secretes GRN, which is growth factor granulin. The process involves CD11b+/Gr1+ myeloid cells that were found to facilitate tumour-assocoated angiogenesis and to render tumours refractory to inhibitions by anti-VEGF treatment. In addition, through bone marrow cells (BMCs), vascular endothelial growth factor-A and placental growth factor trigger the release of BMCs from the bone marrow into the circulation. Cancer-associated fibroblasts are abundant in most carcinomas and are linked to tumour angiogenesis. For example, in breast cancer, cancer-associated fibroblasts release CXCL12 into the blood stream in people affected by breast cancer. CXCL12 releases progenitor cells into the circulation, which results in TME gathering and then promotion of angiogenesis. Platelets at as a long-range delivery system between aggressively growing tumours and tumors that are in a far distance. When VEGFR2+ BMCc and cytokines are taken up by platelets, then angiogenesis is promoted at metastatic sites. Some important cytokines that are involved with angiogenesis at metastatic sites are VEGF, TGF-beta1, PDGF-BB, PIGF, IL-6, and CXCL1. The platelets take up these factors
Another process of metastasis involves affecting BMCs. BMCs are bone marrow cells. When bone marrow cells secrete GRN, a CAF phenotype is adopted. CAF is a cancer-associated fibroblast, leading to expression of pro-inflammatory and matrix remodeling genes and upregulation of GFF15. It also promotes recruitment of circulating inflammatory cells to the tumor site, which results in tumor progression (metastasis).
Manipulation of the extravasation state in the EMT system would help stop metastasis. If extravasation is stopped, then tumor cells would not be able to escape circulation, which would stop metastasis. In addition, if cancer-associated fibroblasts of angiogensis are stopped and are not able to release CXCL12 into the bloodstream, then progenitor cells would not be released into the circulation. Therefore the promotion of angiogenesis in metastatic tumors would not occur. In addition, with bone marrow cells, halting cancer-associated fibroblasts would stop tumor progression (metastasis) because the expression of pro-inflammatory genes and the recruitment of circulating inflammatory cells would not occur.