Abstract
Myeloma cells as well as other hematopoietic cells exist in the bone marrow (BM), where adhesion molecules, cytokines and chemokines may play very important roles in regulating the survival, proliferation and lodgment of myeloma cells.
Galectin-1(Gal-1) is a 14 KDa protein with the binding affinity to the molecules which carry β galactosides in their structure such as CD3, CD4, CD7, CD43, CD45 and integrins. Although Gal-1 is considered to be ubiquitously present in the BM, it remains to be clarified what is the effect of Gal-1 on the survival of myeloma cells. First, we confirmed that Gal-1 as well as SDF-1 was ubiquitously present in the extracellular space of BM samples from MM patients by the immunohistochemical staining.
Furthermore, the expression of Gal-1 gene was found in a BM stromal cell line, KM-102, and also in primary myeloma cells as well as myeloma cell lines, while the expression of SDF-1 gene was detected in KM-102 cells but not in myeloma cells. In the serum-free culture in vitro, Gal-1 could support the survival of primary myeloma cells in the combination with IL-6 and SDF-1 at least for 2 weeks. In order to clarify the mechanism of the effect of Gal-1, we examined the effect of Gal-1 on the survival of myeloma cell lines and B cell l,ines; Ga-1 could support the survival of CD45- U266 and KMS-5 cells, but not support and suppress the survival of B cell lines (Raji and KUS cells) which express CD45, CD45RA and CD45RB but not CD45RO. By using the transfectants of CD45RA, CD45RB or CD45RO in U266 cells, we confirmed that Gal-1 could suppress the survival of CD45RA+ U266 cells as well as B cell lines but not of CD45RB or CD45RO transfectants of U266 cells. These data confirmed that Gal-1 could bind to the CD45RA molecule more effectively than CD45RB or CD45RO. We also revealed that Gal-1 stimulation inhibited the phosphorylation of ERK1/2 in CD45RA+ U266 cells as well as B cell lines, while in CD45- myeloma cells as well as CD45RO+ myeloma cells Gal-1 induced the activation of Akt. Therefore, these data suggest that Gal-1 plays an important role in the supporting the survival of myeloma cells but not B cells in the BM microenvironment.
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