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Human bone marrow heparan sulfate induces leukemia cell differentiation
S D Luikart1, P M Kenney, T R Oegema
1Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Connective Tissue Research
|January 1, 1995
Summary
A specific heparan sulfate proteoglycan from bone marrow stroma can induce myeloid leukemia cell maturation. Minor structural differences in heparan sulfate chains may explain this crucial differentiation activity.
Area of Science:
- Biochemistry
- Cell Biology
- Hematology
Background:
- Hematopoietic cell development is closely linked to the bone marrow stroma.
- Heparan sulfate is a key component of the bone marrow stroma, influencing cell behavior.
Purpose of the Study:
- To isolate and characterize heparan sulfate proteoglycans from human bone marrow stromal cells.
- To investigate the role of these proteoglycans in inducing differentiation of myeloid leukemia cells.
Main Methods:
- Isolation of heparan sulfate proteoglycans from an in vitro human stromal cell line using [35S]sulfate labeling.
- Characterization of proteoglycan hydrophobicity and glycosaminoglycan chain properties (size, charge density).
- Assessment of the ability of isolated proteoglycans to induce maturation of the HL-60 myeloid leukemia cell line.
Main Results:
- A hydrophobic heparan sulfate proteoglycan, anchored by a phosphatidylinositol moiety, was isolated and found to induce HL-60 cell maturation.
- A less hydrophobic heparan sulfate proteoglycan, with similar glycosaminoglycan chain size and charge density, did not induce maturation.
- Structural analysis revealed subtle differences in the carbohydrate sequences of the two heparan sulfate forms.
Conclusions:
- A specific membrane-bound heparan sulfate proteoglycan from bone marrow stroma possesses differentiation-inducing activity for myeloid leukemia cells.
- Minor structural variations in heparan sulfate glycosaminoglycan chains may be responsible for differences in biological function.
- Further research is needed to elucidate the precise relationship between heparan sulfate structure and its role in hematopoietic cell differentiation.