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Insulin-like growth factor binding proteins-2 and -4 enhance the migration of human CD34−/CD133+ hematopoietic stem and progenitor cells
Ist Teil von
International journal of molecular medicine, 2010-01, Vol.25 (1), p.89-96
Ort / Verlag
Greece: D.A. Spandidos
Erscheinungsjahr
2010
Quelle
MEDLINE
Beschreibungen/Notizen
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 IGFBPs 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.