The Concept of a Preniche for Localization of Future Metastases

Abstract

The hypothesis of metastatic niches (advanced kind of “seed and soil” hypothesis) is very promising concept. It has been proposed to supplement the metastatic niche concept with a stage of “preniche” that determines the site of development of a premetastatic niche and of a subsequent metastasis. The “preniche” includes all cellular and molecular events in the site of a prospective metastasis preceding the entrance of myeloid progenitor cells. The preniche integrates an activation of vascular endothelium of the microcirculatory vessels of target organs in the site of a future metastasis under conditions of chronic persistent productive inflammation that can be induced by cytokines from the primary tumor and independently of it. The endothelium activation is responsible for adhesion and clustering of the recruited myeloid progenitor cells and also for the retention of cells of malignant tumors. The preniche easily arises in organs enriched with organ-specific macrophages (lungs, liver, brain, etc.) where the endothelium is predisposed for intensive recruiting of myeloid progenitor cells of macrophages, especially under conditions of inflammation. The feature of CNS is especial population of macrophage cells (microglia) which could be activated and to form metastatic niches without recruiting myeloid progenitor cells and preniche formation as well as bone morrow. Nevertheless, inflammatory prenicha seems to be the factor enhancing brain metastases by the recruiting of additional niche cells and cells of a tumor. Introduction of the preniche concept allows us to avoid difficulties associated with the development of the metastatic niche concept, especially concerning the problem of organ-preferential localization of metastases, and to make potential approaches for preventing metastasizing in some oncologic patients.