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Preniche as Missing Link of the Metastatic Niche Concept Explaining Organ-Preferential Metastasis of Malignant Tumors and the Type of Metastatic Disease

V. M. Perelmuter1,2 and V. N. Manskikh3*

1Cancer Research Institute, Siberian Branch of Russian Academy of Medical Sciences, ul. Savinykh 12/1, 634028 Tomsk, Russia

2Siberian State Medical University, Moskovskii Trakt 2, 654050 Tomsk, Russia; E-mail: pvm@ngs.ru

3Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, Russia; E-mail: manskikh@mail.ru

* To whom correspondence should be addressed.

Received April 27, 2011; Revision received September 18, 2011
Here we attempt 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. 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 some predictions for experimental verification and potential approaches for preventing metastasizing in some oncologic patients.
KEY WORDS: preniche, organ-preferential metastasizing, metastatic niches

DOI: 10.1134/S0006297912010142