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The process that cancer cells undergo to be able to spread throughout the body is called metastasis, the metastasis mechanism explains the successive events that lead to the formation of new secondary tumours in other organs and tissues of the body.
Briefly, cancer cells undergo genetic changes that enables them to move through the blood and lymphatic vessels to create new tumours following the following 8 steps:
Genetic changes
Cancer cells acquire genetic mutations that enable them to detach from the primary tumour and invade nearby tissues. These mutations can affect cell adhesion molecules, signaling pathways, and cytoskeletal components, allowing cancer cells to break free from the tumour mass.
Epithelial-mesenchymal transition (EMT)
During EMT, cancer cells undergo a series of molecular changes that alter their characteristics. They lose their epithelial features, such as cell-cell adhesion, and acquire mesenchymal traits, including increased motility and invasiveness. This transition enhances their ability to migrate through tissues, invade surrounding structures, and colonize distant organs.
Circulation survival
Cancer cells that enter the bloodstream or lymphatic vessels face challenges such as shear forces generated by the flowing blood or lymphatic fluid and immune surveillance. However, some cancer cells can survive these harsh conditions by adapting their physical properties and evading immune recognition, allowing them to circulate in the body.
Extravasation
When cancer cells reach specific sites in distant organs, they undergo extravasation (escaping). This process involves interactions between cancer cells, endothelial cells lining the blood vessels, and extracellular matrix components. Cancer cells use adhesion molecules and enzymes to breach the vessel walls and migrate into the surrounding tissue.
Microenvironment adaptation
After extravasation, cancer cells encounter a new microenvironment with different biochemical and physical characteristics. To establish themselves, cancer cells adapt to the local conditions by secreting enzymes that degrade the extracellular matrix, facilitating invasion and creating space for growth.
Angiogenesis
To ensure a sufficient blood supply for their growth and survival, cancer cells induce angiogenesis, the formation of new blood vessels. They secrete signaling molecules that stimulate nearby endothelial cells to proliferate and form new blood vessels, providing the necessary nutrients and oxygen for tumour expansion.
Immune evasion
Cancer cells have developed various
mechanisms to evade the immune system. They can regulate molecules involved in immune recognition, inhibit immune cell function through the secretion of immunosuppressive factors, or even hijack immune cells to create a favorable microenvironment that supports tumour growth.
Secondary tumour formation
Over time, cancer cells that have successfully undergone
metastasis form secondary tumours, known as metastases, in different parts of the body such as bones, brain or lymph nodes.
These metastases can impair organ function and contribute to the clinical progression of the disease.
Furthermore, metastatic tumours often exhibit genetic and phenotypic heterogeneity, this means that these new tumours develop different characteristics from the original tumour, making them more challenging to treat and more resistant to therapies that were effective against the primary tumour.
Team Let's Biologue
References
Castaneda, M., den Hollander, P., Kuburich, N. A., Rosen, J. M., & Mani, S. A. (2022). Mechanisms of cancer metastasis. Seminars in Cancer Biology, 87, 17–31. https://doi.org/10.1016/J.SEMCANCER.2022.10.006
Fares, J., Fares, M. Y., Khachfe, H. H., Salhab, H. A., & Fares, Y. (2020). Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduction and Targeted Therapy 2020 5:1, 5(1), 1–17. https://doi.org/10.1038/s41392-020-0134-x
Hunter, K. W., Crawford, N. P. S., & Alsarraj, J. (2008). Mechanisms of metastasis. Breast Cancer Research : BCR, 10(Suppl 1), S2. https://doi.org/10.1186/BCR1988
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