Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Long-term bone marrow cultures (LTBMC) from patients with multiple myeloma (MM) and normal donors were analyzed for immunophenotype and cytokine production. Both LTBMC adherent cells from myeloma and normal donor origin expressed CD10, CD13, the adhesion molecules CD44, CD54, vascular cell adhesion molecule 1, very late antigen 2 (VLA-2), and VLA-5, and were positive for extracellular matrix components fibronectin, laminin, and collagen types 3 and 4. LTBMC from myeloma patients and normal donors spontaneously secreted interleukin-6 (IL-6). However, levels of IL-6 correlated with the stage of disease; highest levels of IL-6 were found in LTBMC from patients with active myeloma. To identify the origin of IL-6 production, LTBMC from MM patients and normal donors were cocultured with BM-derived myeloma cells and cells from myeloma cell lines. IL-6 was induced by plasma cell lines that adhered to LTBMC such as ARH-77 and RPMI-8226, but not by nonadhering cell lines U266 and FRAVEL. Myeloma cells strongly stimulated IL-6 secretion in cocultures with LTBMC adherent cells from normal donors and myeloma patients. When direct cellular contact between LTBMC and plasma cells was prevented by tissue-culture inserts, no IL-6 production was induced. This implies that intimate cell-cell contact is a prerequisite for IL-6 induction. Binding of purified myeloma cells to LTBMC adherent cells was partly inhibited by monoclonal antibodies against adhesion molecules VLA-4, CD44, and lymphocyte function-associated antigen 1 (LFA-1) present on the plasma cell. Antibodies against VLA-4, CD29, and LFA-1 also inhibited the induced IL-6 secretion in plasma cell-LTBMC cocultures. In situ hybridization studies performed before and after coculture with plasma cells indicated that LTBMC adherent cells produce the IL-6. These results suggest that the high levels of IL-6 found in LTBMC of MM patients with active disease are a reflection of their previous contact with tumor cells in vivo. These results provide a new perspective on tumor growth in MM and emphasize the importance of plasma cell-LTBMC interaction in the pathophysiology of MM.
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PMID:Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term bone marrow cultures. 791 45

Human multiple myeloma (MM) xenografts have been difficult to establish in athymic mice. We examined the feasibility of establishing human MM xenograft growth in SCID mice following subcutaneous (sc) injection of 1-2 x 10(7) cells from the human plasma cell dyscrasia (PCD) cell lines RPMI 8226 and ARH-77. SC tumors emerged in 67% (6/9) of RPMI 8226- and 6 of 6 ARH-77-injected mice after a latency period of 9-54 days, and reached 19-35 mm in diameter before the mice were sacrificed. RPMI 8226 and ARH-77 primary tumor DNA hybridized positively with the human genome probe Alul-(Blur8), confirming successful engraftment of the human MM cell lines. The RPMI 8226 xenografts comprised predominantly of plasmacytoid cells that expressed the relevant cytoplasmic immunoglobulin (cIg) light chain isotype. Xenografted RPMI 8226 cells also expressed CD10 (CALLA; 44% reactive cells), CD38 (OKTIO; 69%), CD5 (49%), and reacted with the MM monoclonal antibody MM4 (39%). Human MM growth appeared to be localized subcutaneously for both RPMI 8226 and ARH-77 xenografts. There were no detectable metastatic foci in kidney, brain, heart, or bone marrow. Whereas diffuse plasma cell infiltrates were observed in spleen, GI tract, and lung biopsies of tumor-bearing mice, these infiltrates were of host origin according to immunophenotyping and DNA analyses. Neither the originating RPMI 8226 line nor its SCID mouse xenograft expressed Epstein Barr virus (EBV) genome sequences. These observations indicate that both EBV- (RPMI 8226) and EBV+ (ARH-77) cell lines can be successfully propagated in SCID mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heterotransplantation of human multiple myeloma cell lines in severe combined immunodeficiency (SCID) mice. 839 Dec 43