**2.11. Is ECM the main constituent of niches?**

Despite the "skill" they display in moving away from the site in which they were first formed, tumor cells are rather ineffective in terms of forming colonies in distant organs. Millions of cells drop off even from small tumors every single day; even though macroscopic metastases have not developed, it is possible to identify these cells in the blood circulation and in small foci in the bone marrow. The dormant state of micrometastases, which is defined as the capacity to preserve their existence for a long period without any progression, was observed in breast and prostate cancer [29, 30, 44].

In the studies demonstrating that ECM undertook a dynamic niche role in the progression of cancer in recent years [5–7], investigators indicated that the microenvironment or niche played a major role in the development of cancer. Abnormal ECM directly promotes cellular trans‐ formation and metastasis and impacted the progression of cancer [84].

A successful metastasis does not require local niche supporting only cancer cell development in the primary focus, but also necessitates the survival, colonization of the cancer cells invading the metastatic niches and their achievement of macrometastasis [85–87].

The molecular mechanisms of colonization have just begun to be enlightened in mice models, but the view claiming that tumor cells impact normal stroma cells and secrete cytokines, growth factors and proteases, which transform the site of metastasis into an environment where cancer cells may live, appears to be suitable [88, 89].
