VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche
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...Some of these cells may already be targeted to the premetastatic niche in response to tumor-generated inflammatory signals prior to the arrival of metastasis-initiating cancer cells (Kaplan et al., 2005)....
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...Recruitment of such cells may be a consequence of tumor necrosis, but as mentioned above certain carcinomas actively secrete factors that upregulate fibronectin and cause migration of VEGF receptor 1 (VEGFR1)-positive hematopoietic progenitors to the premetastatic niche (Kaplan et al., 2005)....
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...Soluble factors released from the primary tumor appear to trigger the formation of a metastatic niche that is induced initially by the expression of embryonic-type fibronectin, which is most likely produced by fibroblasts at these sites (Kaplan et al., 2005)....
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...Indeed, MMP-9 turns out to be critical for the formation of the metastatic niche (Kaplan et al., 2005), which is most likely linked with its ability to liberate VEGF and thereby support angiogenesis (Bergers et al., 2000)....
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...MMP-9 releases soluble Kit-ligand to recruit stem and progenitor cells from the bone marrow (Heissig et al., 2002), which may be of particular significance in this context, given that the niche-forming progenitor cells express c-Kit (Kaplan et al., 2005)....
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...In fact, MMP-2, -3, and -9 have already been shown to contribute to the establishment of metastasis-prone sites at tumor-distant organs (Erler et al., 2009; Huang et al., 2009; Kaplan et al., 2005)....
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...Recent findings suggest that metastatic tumor cells specifically localize to receptive sites, called premetastatic niches, in a complex interplay with inflammatory cells and hematopoietic progenitor cells (Kaplan et al., 2005)....
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References
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