Pre-metastatic niche formation is influenced by many different bodily processes, including the suppression of the immune system[4] and an increase in the presence of cytokines and other growth factors.
There are often tumor cell deposits found in organs without a metastasis, indicating that metastases do not always proliferate in the tissues that they enter after leaving the circulatory system.
[4] Given their important role not only in protecting the growing metastasis from immune system attacks, but also in enabling extravasation, myeloid cells are a key factor in the development of the pre-metastatic niche, and thus eventually in promoting metastases.
[9] The primary tumor, in an attempt to evade detection by the immune system, uses chemokines in order to increase recruitment of bone marrow-derived myeloid cells to secondary organs.
In addition, cancer cells from the primary tumor can be used to induce inflammation in the future site of the pre-metastatic niche in the secondary organ, which is similar to the immune response created by an infection.
Specifically, necessary amino acids are depleted and lymphocyte movement is decreased while regulatory T cells, which suppress the immune system, and oxidative stress are increased.
Since tumor growth is often difficult in a new and relatively hostile environment, metastasis had been considered by many to be an inefficient process, despite its high mortality rate.
One such possibility is employing methods that attempt to limit the expression of VEGFR1 in cells, thereby combating metastasis by delaying the creation of or eradicating the pre-metastatic niche altogether.