Osteopontin is an adhesive factor for myeloma cells and is found in increased levels in plasma from patients with multiple myeloma.
OBJECTIVE
Osteopontin (OPN) is a non-collagenous matrix protein produced by various cells including osteoblasts, osteoclasts and several types of tumor cells. It is involved in a number of physiologic and pathologic events including adhesion, angiogenesis, apoptosis, inflammation, wound healing and tumor metastasis. We wanted to investigate the potential role of OPN in multiple myeloma.


METHODS
Myeloma cells and stromal cells from myeloma patients were investigated as potential OPN-producers. Furthermore, OPN was tested in proliferation, migration and adhesion assays with myeloma cells. Serum and plasma OPN in myeloma patients were measured by enzyme-linked immunosorbent assay (ELISA). OPN levels were correlated to disease variables at diagnosis and to disease outcome.


RESULTS
Myeloma cells produce OPN, and stromal cells from myeloma patients express higher levels of OPN than stromal cells from healthy controls. The myeloma cell lines ANBL-6 and INA-6 adhered to OPN. NOD/SCID mice inoculated with OPN-producing ANBL-6 cells had elevated levels of murine OPN in serum, whereas human OPN was not detectable. Plasma and serum levels of OPN were significantly higher in myeloma patients than in healthy individuals. Interpretation and Conclusions. Myeloma cell lines adhere to OPN, indicating that elevated stromal expression of OPN may be one of the factors responsible for the retention of myeloma cells in the bone marrow. The elevated plasma OPN levels in myeloma patients could be due to both production of OPN by the tumor cells and tumor-induced production of OPN by non-tumor cells.
Standal
Therese
T
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Hjorth-Hansen
Henrik
H
Rasmussen
Thomas
T
Dahl
Inger Marie S
IM
Lenhoff
Stig
S
Brenne
Anne-Tove
AT
Seidel
Carina
C
Baykov
Vadim
V
Waage
Anders
A
Børset
Magne
M
Sundan
Anders
A
Hjertner
Oyvind
O
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002455:Cell Division; D045744:Cell Line, Tumor / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D002465:Cell Movement; D017077:Culture Media, Conditioned / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000235:genetics / Q000473:pathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism; D053495:Osteopontin; D010265:Paraproteinemias / Q000097:blood; D011828:Radiation Chimera; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms; D017154:Stromal Cells / Q000378:metabolism; D016896:Treatment Outcome
D017077:Culture Media, Conditioned; D009363:Neoplasm Proteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin