Preparing the "Soil": The Premetastatic Niche

Cell and Developmental Biology, Cornell University, Итак, New York, United States
Cancer Research (Impact Factor: 9.33). 01/2007; 66(23):11089-93. DOI: 10.1158/0008-5472.CAN-06-2407
Source: PubMed


Current focus on cancer metastasis has centered on the intrinsic factors regulating the cell autonomous homing of the tumor cells to the metastatic site. Specific up-regulation of fibronectin and clustering of bone marrow-derived cellular infiltrates coexpressing matrix metalloproteinases in distant tissue sites before tumor cell arrival are proving to be indispensable for the initial stages of metastasis. These bone marrow-derived hematopoietic progenitors that express vascular endothelial growth factor receptor 1 mobilize in response to the unique array of growth factors produced by the primary tumor. Their arrival in distant sites represents early changes in the local microenvironment, termed the "premetastatic niche," which dictate the pattern of metastatic spread. Focus on the early cellular and molecular events in cancer dissemination and selectivity will likely lead to new approaches to detect and prevent metastasis at its earliest inception.

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    • "Recent studies on the metastatic process have suggested that the tumor micro- and macro-environments may play critical roles in metastatic dissemination [reviewed in Ref. (172, 173)]. One of the more novel concepts is that of the pre-metastatic niche, where the innate immune system plays a key role (41, 42, 174). Attenuation of NK cell activity is associated with generation of the pre-metastatic niche and metastasis efficiency in murine models (40), where conditioned media from hypoxic tumor cells was associated with increased NK recruitment and reduced NK cytolytic activity. "
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    • "The implanted fragments are poorly vascularized and the bone marrow compartment is mainly filled with adipocytes and connective tissue instead of haematopoietic cells [17e19]. Although a series of genetic and epigenetic alterations of cancer cells may be necessary for initial carcinogenesis, it is nowadays widely accepted that for the development of overt metastases a permissive niche is required [20] [21]. Disseminated cancer cells directly compete with haematopoietic stem cells (HSCs) for the occupancy of their niche and changes of the microenvironment alter cancer cell dissemination [8]. "
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