Insulin-like growth factor binding proteins-2 and-4 enhance the migration of human CD34-/CD133+ hematopoietic stem and progenitor cells

The insulin-like growth factor (IGF) system is involved in cell migration, which plays an important role in cancer progression. It has been shown that cancer progression correlates with the level of circulating human hematopoietic stem and progenitor cells (HSPCs) expressing CD34 and/or CD133. However, it is unknown whether factors released from cancer cells, including soluble compounds of the IGF system, recruit these HSPCs via enhancing their migration. Our study showed the expression of type I IGF receptor (IGF-IR) in human HSPCs expressing CD34 and/or CD133. In an indirect co-culture model, soluble factors released from human lung epithelial cancer cells (H358, H322) increased the migration of CD34(-)/CD133(+) cells towards cancer cells, whereas migration of CD34(+)/CD133(+) or CD34(+)/CD133(-) cells remained unchanged. The lung epithelial cancer cell lines H358 and H322, exhibited a high expression of IGFBP-2, -4 and -6 but not IGF-I and IGFBP-3. Subsequent analyses with those soluble compounds of the IGF system revealed a dose-dependent stimulating effect of the IGFBP-2 and -4 on the migration of CD34(-)/CD133(+) cells. In contrast, IGF-I and IGFBP-3 and -6 did not influence the migration of CD34(-)/CD133(+) cells. Because IGEBPs are involved in cell migration via IGF-dependent and -independent mechanisms, our study indicates that IGFBP-2 and -4, which are expressed in lung epithelial cancer cells, enhance the migration of CD34(-)/CD133(+) HSPCs independent of IGF-I.