Publication Date:
2005-11-16
Description:
Human sulfatases Hsulf-1 and Hsulf-2 are extracellular endosulfatases that specifically remove 6-O sulfates from heparan sulfate chains. Published studies have shown that expression of Hsulf-1 in some tumor cell lines diminishes their response to heparin-binding growth factors (e.g., FGF-2, HGF) leading to speculation that these enzymes may regulate tumor growth. To examine this possibility in vivo, the cDNA for either Hsulf-1 or Hsulf-2 was expressed in the human myeloma cell line CAG. Disaccharide composition analysis of heparan sulfate chains isolated from the surface of the transfected cells reveals that 6-O sulfation of trisulfated disaccharides is diminished by 70% and 50% on cells expressing Hsulf-1 and Hsulf-2, respectively, as compared to control cells transfected with empty vector only. When stimulated with exogenous FGF-2, downstream signaling as measured by the level of phosphorylated ERK1/2, is reduced in HSulf-1 or Hsulf-2 transfectants as compared to controls. To determine if Hsulf-1 and Hsulf-2 regulate myeloma tumor cell growth in vivo, cells were injected subcutaneously into the left flank of SCID mice. Monitoring of whole animal tumor burden by analysis of human kappa light chain present in the serum revealed that tumors formed from cells expressing either Hsulf-1 or Hsulf-2 exhibited a dramatic inhibition of tumor growth as compared to tumors formed from control cells (p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
Permalink