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In the history of cancer research, the concept of tumors and their metastasis has changed significantly.In 1863, German pathologist Rudolf Virchow first proposed the link between inflammation and cancer, paving the way for the later concept of tumor microenvironment (TME).However, what really introduced the relationship between the tumor microenvironment and cancer metastasis into scientific discussion was the "seed and soil" theory proposed by Stephen Paget in 1889. This theory not only illustrates the metastasis trend of cancer cells, but also emphasizes the complex relationship between the tumor and its surrounding microenvironment.
If tumor cells want to metastasize successfully, they must grow in the right microenvironment, just like seeds need fertile soil to germinate and grow.
As time goes by, scholars in the field of oncology have deepened their understanding of this theory.In 1928, James Ewing challenged Padger's idea, advocating that the ability of cancer cells to metastasis is mainly affected by anatomical and hemodynamic factors, and pointed out that tumor cells are more likely to stay in the first connected organ, which is not entirely dependent on the surrounding tissue environment.This view suggests that traits or mutations within tumor cells may play a central role in their metastatic potential.
In the 1970s, Isaiah Fidler's research extended this field further, with a complementary hypothesis he proposed that emphasized the mechanical aspects of blood flow and specific metastasis of certain organs.
The metastasis of tumors is not only physical movement with blood flow, but also targets specific organs.
In recent years, scientists have begun to pay attention to the role of lymphocytes in the tumor microenvironment, and studies have shown that the activities of tumor-infiltrating T cells and B cells, as well as the natural killer (NK) cells, are closely related to tumor characteristics.Tumor-infiltrated T cells were found to have strong anti-tumor functions, but under the inhibition of the tumor microenvironment, their cytotoxicity seemed insufficient.
The importance of the vascular system
The growth of tumors is closely related to their vascular system, because blood vessels provide tumors with oxygen, nutrition and growth factors.When the tumor diameter is less than 1-2 mm, oxygen and nutrients can be supplied through passive diffusion.However, as the tumor grows, the center part often stays away from the existing blood supply, resulting in hypoxia and acidification of the tumor microenvironment.In this case, the tumor promotes angiogenesis, and this process is closely related to the degree of malignancy of the tumor.
The upregulation of angiogenesis allows cancer cells to continue to grow, which is considered one of the characteristics of cancer.
Immune cells in the tumor microenvironment
Immune cells in the tumor microenvironment can be divided into tumor-promoting and tumor-inhibiting.These cells, such as myelogenic inhibitor cells and tumor-associated macrophages, have properties that promote tumor growth, while some immune cells such as cytotoxic T cells and natural killer cells can inhibit tumor growth.However, due to the influence of the tumor microenvironment, many immune cells with anti-tumor ability will be inhibited, allowing the tumor to grow further.
For example, myelogenic inhibitory cells can affect T cell responses, promote angiogenesis and support metastasis.Tumor-related macrophages are mostly M2 phenotypes. As the tumor develops, their number and activity are also increasing, and are regarded as the link between tumors and inflammatory responses.
The presence of tumor-associated macrophages is closely related to poor prognosis, which in turn improves tumor cell survival by providing a microenvironment that promotes metastasis.
Summary
By reviewing the challenges from Wercho’s discovery to Ewing’s challenges, to modern in-depth research on the tumor microenvironment, we can understand that tumor metastasis is a multifactorial interaction process, and future therapeutic strategies need to consider these complex biological environments.In the medical community, it is necessary to continue to explore these dynamic factors and how they play a role in tumor progression, thereby developing more effective treatments.Do we really understand all the relationship between tumors and their microenvironment and can make the most of this knowledge to improve treatment results?
