title: The regulatory mechanism of IL-6-dependent proliferation of human myeloma cells.
abstract: Multiple myeloma (MM) is a malignant tumor of plasma cells in the bone marrow. Interleukin 6 (IL-6) is an indispensable growth factor for myeloma cells. The heterogeneity of myeloma cells are the characteristics of MM, categorized into five sub-populations, two immature cells, MPC-1<PRE>-</PRE> CD49e<PRE>-</PRE> CD45<PRE>+/-</PRE>, intermediate cells, MPC-1<PRE>+</PRE> CD49e<PRE>-</PRE> CD45<PRE>+/-</PRE>, and mature cells, MPC-1<PRE>+</PRE> CD49e<PRE>+</PRE> CD45<PRE>+</PRE>. Only MPC-1<PRE>-</PRE> CD49e<PRE>-</PRE> CD45<PRE>+</PRE> immature cells (∼2% of total myeloma cells) respond to IL-6 to proliferate. CD45 protein tyrosine phosphatase is the determinant of IL-6 dependent cell growth of myeloma cells, although well studied IL-6 signal transducing factors, such as, IL-6Ra, gp130, Jak2, STAT3, and MAPK, are activated and involved in the process. Immature CD45<PRE>-</PRE> cells converted to CD45<PRE>+</PRE> cells after IL-6 stimulation both in U266 cells and sorted myeloma cells from the bone marrow aspirates of MM patients. CD45<PRE>-</PRE> cells are relatively resistant to serum starvation compared to CD45<PRE>+</PRE> cells. Because IL-6 level in the bone marrow is low even in MM patients, the CD45<PRE>-</PRE> phenotype of myeloma cells may protect the cells from apoptosis. These findings of a tuning effect of CD45 on myeloma cell proliferation may aid the study of IL-6 dependent proliferation of myeloma cells and lead to the development of new therapies for MM patients.
authors.affiliation: Department of Bio-Signal Analysis, Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Tsuyama
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Saeid
authors.initials: S
authors.lastname: Abroun
authors.forename: Shangqin
authors.initials: S
authors.lastname: Liu
authors.forename: Fu-Jun
authors.initials: FJ
authors.lastname: Li
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Otsuyama
authors.forename: Xu
authors.initials: X
authors.lastname: Zheng
authors.forename: Masanori
authors.initials: M
authors.lastname: Obata
authors.forename: Osamu
authors.initials: O
authors.lastname: Taniguchi
authors.forename: Michio M
authors.initials: MM
authors.lastname: Kawano
mesh_terms: D048708:Cell Growth Processes / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015850:Interleukin-6