On the one hand systemic release of tumor-derived factors can downregulate CXCR4 resulting in the proliferation and mobilization of HSPCs like VEGFR1+ HSPCs, myeloid cell skewed LSKs and α-SMA+ cancer-associated fibroblasts activating Sca-1+c-Kit- cells to the premetastatic niche (104, 111–113). This evidence concerns the gene FLT1 and neoplasm.