Study on the molecular mechanism of defective SDF-1 response in leukemic cells
Date Issued
2004
Date
2004
Author(s)
Chen, Ya-Ying
DOI
zh-TW
Abstract
Immature hematopoietic cells are normally entrapped in the bone marrow (BM) until differentiation into mature ones. Recent reports indicated that the CXC chemokine SDF-1 and its receptor, CXCR4, play a key role in retaining haematopoietic progenitor cells (HPCs) within the BM and mobilization of HPCs. In contrast to normal HPCs, immature leukemic cells often egress into peripheral blood (PB) with unclear mechanisms. We speculate that impaired CXCR4/SDF-1 chemotaxis axis may play a role in this scenario.
We previously studied the expression of CXCR4 and responses toward SDF-1 in six leukemic cell lines (HL-60, HL-CZ, U937, Raji, Jurkat, and K562). We found that U937 and Jurkat had high CXCR4 expression and good response to SDF-1; HL-60 and Raji had high CXCR4 expression but poor response to SDF-1; while K562 and HL-CZ had low CXCR4 expression and poor response to SDF-1.
The possible mechanism of the defective SDF-1-response was further explored. We found that fibronectin did not correlate with the poor response to SDF-1 in Raji and HL-60 cell lines. We demonstrated that Raji cells had defect in the process of CXCR4 receptor endocytosis, but there was phosphorylation of CXCR4 in Raji cells after treatment of SDF-1. HL-60 cell had the defect in CXCR4/SDF-1 signaling pathway, although there was perfect function of internalization. Comparing to other leukemic cell lines, the K562 and HL-CZ leukemic cell lines had lower level of CXCR4 mRNA, but still had substantial intracellular CXCR4 protein, suggesting the defective membrane translocaiton for CXCR4 protein. The result of western blot analysis showed that the molecular weight (MW) of CXCR4 in both HL-CZ and K562 cells was 40 kDa, while the predicted MW of glycosylated CXCR4 is 45-47 kDa. It suggested an incompletion that the modification of CXCR4 in HL-CZ and K562.
We concluded that dysfunction of the CXCR4/SDF-1 signaling axis may be responsible for egression of immature leukemic cells into peripheral circulation.
Subjects
血癌細胞
趨化激素SDF-1
SDF-1
leukemic cell
Type
other
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