Dipeptide γ-d-Glu-d-Trp (thymodepressin) inhibits migration of Cd34+ cells from the bone marrow into peripheral blood during tumor growth

Abstract

We studied the effect of dipeptide gamma-d-Glu-d-Trp (thymodepressin) on migration of CD34+ hemopoietic precursors and their direct adhesion to fibronectin in tumor-bearing mice on days 8, 11, 15, and 17 of tumor growth and on expression of CXCR-4 (CD184+) to SDF-1 and integrin beta1 (CD29+) by bone marrow cells. In tumor-bearing mice treated with gamma-d-Glu-d-Trp, the percent of CD34+ hemopoietic precursors in the peripheral blood considerably decreased throughout the observation period; the content of CD34+ hemopoietic precursors in the tumor tissue was 2-3-fold below the control against the background of increased content of CD34+ cells in the bone marrow. In animals treated with the peptide, the content of cells expressing CXCR-4 in the peripheral blood, bone marrow, and tumor tissue significantly decreased, while the percent of cells expressing integrin beta1 receptor (CD29+) in the bone marrow increased 2-fold, which was paralleled by an almost 2-fold increase in the percent of cells binding to fibronectin. We hypothesized that dipeptide gamma-d-Glu-d-Trp suppressed mobilization/migration of CD34+ hemopoietic precursor cells from the bone marrow to the peripheral blood of tumor-bearing mice.

Decreased Intracellular pH Induced by Cariporide Differentially Contributes to Human Umbilical Cord-Derived Mesenchymal Stem Cells Differentiation

“…It is well known that pH i is important for cell metabolism since many cellular mechanisms are sensitive to changes in pH i [25,26,27,28]. In normal differentiated adult cells, pH i is generally ∼7.2.…”

Orphan lysosomal solute carrier MFSD1 facilitates highly selective dipeptide transport

“…To date, it is still an open question how these specific dipeptides exported by MFSD1 contribute to the phenotypes observed in the MFSD1 −/− mouse ( 13 ), in MFSD1 −/− tumor cells ( 7 ), and during lymphocyte development and liver homeostasis ( 53 ). Dipeptides have been shown to influence the activity of enzymes ( 54 – 58 ), to affect cell migration ( 59 , 60 ), to play a role as antioxidants ( 61 ), to exhibit antidepressant-like activity ( 62 ), and to be involved in the eradication of cytotoxic lymphocytes ( 63 , 64 ). We speculate that MFSD1 might be implicated in at least some of these actions, and that its function is not limited to providing amino acids for reuse in protein synthesis.…”

The First Reciprocal Activities of Chiral Peptide Pharmaceuticals: Thymogen and Thymodepressin, as Examples

“…Thymodepressin, in vitro and in vivo, affects the initial stages of hemopoiesis, reducing the number of committed CFU-C-8 cells in the S-phase of the cell cycle. As a result, administration of the peptide leads to a dose-dependent transient decrease in the number of leucocytes in the blood of the experimental animal [85].…”