Abnormal expression of hyaluronan synthases in patients with Waldenstrom's macroglobulimenia.
Little is known about the biology or spread of Waldenstrom's macroglobulinemia (WM), a lymphoplasmo-proliferative disorder. Hyaluronan synthases (HASs), plasma membrane proteins, synthesize the extracellular matrix molecule hyaluronan (HA), which plays a role in malignant cell migration and the spread of many cancers. Three isoenzymes of HAS-HAS1, HAS2, and HAS3-are detected in humans. Aberrant expression of the HASs is coupled with different abnormalities. We have analyzed the expression pattern of HASs in WM patients. HAS3 was expressed in all patients and healthy donors tested, whereas the expression of HAS1 and HAS2 varied among the WM patients. Additionally, in WM patients, we have detected novel variants of HAS1, one of which was also detected in multiple myeloma (MM) patients. We speculate that HAS1 variants synthesize the intracellular HA ligand for RHAMM (a receptor for HA). RHAMM contributes to genetic instability in MM; therefore, we speculate that it may also contribute to genetic instability in WM. Furthermore, we suggest that overexpression of HAS1 and its variants in combination with HAS3 may form an HA matrix around WM cells, thus preventing their elimination by the immune system, and it promotes their migration and may facilitate the spread of disease.
Department of Oncology, University of Alberta and Cross Cancer Institute, Edmonton, Alberta, Canada.
Sophia
S
Adamia
Mary
M
Crainie
Jitra
J
Kriangkum
Michael J
MJ
Mant
Andrew R
AR
Belch
Linda M
LM
Pilarski
D018951:Antigens, CD20; D001854:Bone Marrow Cells / Q000201:enzymology; D016326:Extracellular Matrix Proteins; D015870:Gene Expression; D005786:Gene Expression Regulation; D014453:Glucuronosyltransferase / Q000235:genetics*; D016695:Glycosyltransferases; D006801:Humans; D018960:Hyaluronan Receptors; D000076002:Hyaluronan Synthases; D007527:Isoenzymes; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008024:Ligands; D008565:Membrane Proteins; D009101:Multiple Myeloma / Q000201:enzymology / Q000235:genetics; D014166:Transferases; D008258:Waldenstrom Macroglobulinemia / Q000201:enzymology* / Q000235:genetics; D029867:Xenopus Proteins
D018951:Antigens, CD20; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D008024:Ligands; D008565:Membrane Proteins; D029867:Xenopus Proteins; C098946:hyaluronan-mediated motility receptor; D014166:Transferases; D016695:Glycosyltransferases; D014453:Glucuronosyltransferase; C056944:HAS1 protein, Xenopus; C101754:HAS2 protein, human; C105458:HAS3 protein, human; C491096:Has2 protein, Xenopus; D000076002:Hyaluronan Synthases