When cancer cells metastasize, where do they go?
2024-08-06
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A characteristic of advanced cancer is metastasis, where cancer cells escape from the primary site, begin to wander around, and eventually settle down in a new place.Different cancer cells are prone to metastasis to different places. For example, lung cancer is prone to brain metastasis, so when developing new drugs, we hope that the drugs can penetrate the brain, but colorectal cancer rarely metastasizes to the brain, but it is easy to metastasize to the liver, while breast cancer metastasis to the liver, bone, lung and brain are relatively common.Why do different tumors prefer to go to different places? They are all cancer cells, so why do they have specific preferences for their "new homes"?Sometimes it's simply for ease of transfer.Our body is like a country, and each organ is a different city, which is connected by various "highways" and "railways", that is, the blood circulation system and lymphatic circulation system. When tumor cells metastasize, they often go to new places through the circulatory system. If the distance is close and the transportation is convenient, it is easier to metastasize.Blood circulation has a great impact. For example, blood from the intestine usually flows to the liver through the portal vein, so colorectal cancer cells can easily metastasize to the liver through the portal vein, just like a high-speed express train. For similar reasons, pancreatic cancer is also most likely to choose the liver as its new settlement.In addition to the blood, there is also the lymphatic circulatory system, which is another transportation network in the body that cancer cells can use. Breast cancer cells often migrate to the lymph nodes in the armpit through the lymphatic vessels, and then spread to other parts of the body. It's like transferring from one subway station to another. The same is true for prostate cancer, which often first goes to nearby lymph nodes and then spreads to bones.Then, the organ's microenvironment is important.For cancer cells to reach an organ is only the first step; being able to survive is the key, just like when humans spread across the earth, they not only have to go to a place, but also have to adapt to the environment there, find food and ways to survive, before they can take root in one place.picture:Map of early human "transfers"
When studying the relationship between cancer cells and metastatic organs, the most mainstream theory is the "soil-seed" theory.Each organ is like a small ecosystem with its own special soil, and cancer cells are like seeds. Different seeds like different soils, so different cancer cells tend to metastasize to different places. Pancreatic cancer cells adapt to the soil of the liver, so they metastasize to the liver the most.It is conceivable that the more nutritious a place is, the more likely it is to become a target for more cancer cells to metastasize, just like some cities are more livable and people of all kinds want to come. For example, why do many cancers metastasize to the bones? One important reason is that bones are rich in calcium and other minerals, which are the "nutrients" that cancer cells like, allowing them to thrive here. The liver is also an example, where there is a rich blood supply and sufficient nutrition, making it an ideal place for many cancer cells to live.On the other hand, there are almost no metastatic tumors in the heart. Why? Because the environment there is too harsh and not suitable for cancer cells to survive. The blood flow in the heart is very fast, which makes it difficult for metastatic cancer cells to attach and grow on the heart wall. Muscles also have almost no cancer metastasis because its blood flow pattern and metabolic environment are not suitable for the growth of cancer cells, and they are easily starved to death there.At the same time, the characteristics of the tumor cells themselves are also critical.Just as important as the environment are the characteristics of the cells themselves. For example, lung cancer cells particularly like to metastasize to the brain. Why? Because for some unknown reason, they can more easily pass through the protective layer of our brain: the blood-brain barrier, as if they have obtained some kind of special pass, which allows them to enter the brain more easily, but colorectal cancer cells are less capable of this.Malignant melanoma cells seem to be particularly good at "traveling far", often metastasizing to the liver or different parts of the body, probably because they have special "adhesion molecules" that are like strong glue, once they arrive at the right place, they can stick firmly and stay. If cancer cells are very hardy and can survive in different environments, they are more likely to metastasize, just like cockroaches or mice can be seen in every corner of the earth.But another type of skin cancer, basal cell carcinoma, rarely metastasizes. One reason is that these cancer cells are adapted to the specific environment of the skin and have relatively demanding requirements. It is not easy for them to survive and reproduce in other organs. Just like the pandas in Sichuan, they have very specific requirements for food. If they want to move to other places, they can only go to the zoo at most.Finally, there are differences in immunity.For cancer to metastasize, it must escape the immune system, otherwise it will be killed. Different organs have different immune surveillance capabilities, just like some places have a lot of police and some places have fewer police.For example, the spleen has almost no cancer cell metastasis. Why? Because it is an important part of the immune system, full of various immune cells that can quickly identify and attack invading cancer cells. When cancer cells reach the spleen, it is like a thief entering a special forces training unit. It is difficult for him to survive, so how can he start a thief company?On the other hand, the brain is a place where immune surveillance is relatively weak. Normally, the blood-brain barrier prevents cancer cells from entering. But if cancer cells do sneak in, they can easily "hide and seek" here, survive and reproduce quietly.picture:Cancer cells and their living microenvironment
In short, studying the characteristics of cancer cell metastasis is not only a scientific research topic, but also an important idea for developing new treatments and improving the survival rate of cancer patients.The current development of anti-cancer drugs is still mainly focused on the reproduction of cancer cells. There are not many drugs specifically targeting cancer cell metastasis, but I think this is worthy of study.We already know that metastasis is the key cause of death. It is not easy for cancer cells to metastasize because they have to adapt to the new environment and hide from the immune system. Each link is full of challenges and choices, and it can be said that it is a life-and-death struggle. Our goal is to make its metastasis more difficult.The best situation would be “ten deaths and zero survivals”.
*This article is intended to popularize the science behind cancer. It is not a drug promotion material, nor a treatment recommendation. If you need guidance on disease treatment options, please go to a regular hospital for treatment.
references:
1. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer. 2002 May 15;94(10):2698-705.2. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nature Reviews Cancer, 3(6), 453-458.3. Cancer metastasis: building a framework. Cell, 127(4), 679-695.4. Tumor metastasis: mechanistic insights and clinical challenges. Nature Medicine, 12(8), 895-904.5. Tumor metastasis: molecular insights and evolving paradigms. Cell, 147(2), 275-292.Microenvironmental regulation of metastasis. Nature Reviews Cancer, 9(4), 239-252.6. The metastatic niche: adapting the foreign soil. Nature Reviews Cancer, 9(4), 285-293.7. The immunobiology of cancer immunoediting and immunoescape. Immunity, 21(2), 137-148.8. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science, 331(6024), 1565-1570.
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