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The concept of the tumor microenvironment (TME) dates back to 1863 when Rudolf Virchow established a connection between inflammation and cancer. However, it was not until 1889 that Stephen Paget's seed and soil theory introduced the important role of TME in cancer metastasis, highlighting the intricate relationship between tumors and their surrounding microenvironment.
The tumor microenvironment, composed of stromal cells, immune cells and singaling molecules, supports invasion by creating good and favorable conditions for tumor cell migration. [20] For example, cancer- associated fibroblasts (CAFS) produce substances that remodel the ECM and promote cancer progression.
The cancer stem cell model asserts that within a population of tumour cells, there is only a small subset of cells that are tumourigenic (able to form tumours). These cells are termed cancer stem cells (CSCs), and are marked by the ability to both self-renew and differentiate into non-tumourigenic progeny. The CSC model posits that the ...
In order to metastasize, tumor cells should arrive at an organ with an environment conducive to their growth, such as a pre-metastatic niche. The creation of this environment is accomplished by factors from the primary tumor that alter the structure of the secondary organ in order to allow cells from the primary tumor to more easily colonize the secondary organ. [7]
A cancer-associated fibroblast (CAF) (also known as tumour-associated fibroblast; carcinogenic-associated fibroblast; activated fibroblast) is a cell type within the tumor microenvironment that promotes tumorigenic features by initiating the remodelling of the extracellular matrix or by secreting cytokines.
The migration type is predominantly influenced by characteristics of the tissue microenvironment, and is dependent on molecular changes within the tumor cells. Patterns of cancer cell invasion: collective cell and individual cell migration. In collective cell migration, tumor cells exhibit high expression of E-cadherin and integrins.
Another model has been described in tumor cells in an obesity model called Warburg effect inversion. Whereas in the reverse model, the stroma of the microenvironment produces energy-rich nutrients, in a context of obesity these nutrients already exist in the bloodstream and in the extracellular fluid (ECF).
An illustration depicting primary tumor (in the form of tumor microenvironment) and the circulating tumor cells. A circulating tumor cell (CTC) is a cancer cell from a primary tumor that has shed into the blood of the circulatory system, or the lymph of the lymphatic system. [1]