Overexpression of Annexin II affects the proliferation, apoptosis, invasion and production of proangiogenic factors in multiple myeloma

Abstract

The abnormal expression of Annexin II (AnxA2, A2) has been associated with the development of tumors; however, its expression and function in multiple myeloma (MM) is less known. We compared the expression of AnxA2 in primary myeloma cells from MM patients with that in normal plasma cells from normal subjects and found that myeloma cells from patients had higher expression of AnxA2. Expression of AnxA2 was also significantly higher in MM cell lines U266 and RPMI8226, compared with other hematologic tumor cell lines. Transfecting U266 and RPMI8226 cells with the small interfering RNA (siRNA) that targets human AnxA2 led to significant downregulation of AnxA2 expression, which resulted in the decreased proliferation, invasive potential and increased apoptosis of U266 and RPMI8226 cell lines. Silencing AnxA2 gene by siRNA also inhibited the expression of pro-angiogenic molecules including VEGF-C, VEGF-R2, MMP-2, MMP-9, MT1-MMP and TIMP-2 in the two cell lines. Our data suggested that the AnxA2 is overexpressed in MM patients and myeloma cell lines U266 and RPMI8226, and that AnxA2 overexpression appeared to affect the proliferation, apoptosis, invasive potential and production of pro-angiogenic factors in MM cell lines U266 and RPMI8226.

2D-DIGE analysis of phospho-enriched fractions from dasatinib-treated melanoma cell lines

“…ANXA2 siRNA treatment has previously been shown to reduce proliferation and migration and to increase apoptosis in a range of cancer cell types [31][32][33][34][35]. We found that ANXA2 siRNA caused significant inhibition of growth in the dasatinibsensitive WM-115 cells.…”

A HGF/cMET Autocrine Loop Is Operative in Multiple Myeloma Bone Marrow Endothelial Cells and May Represent a Novel Therapeutic Target

“…cMET inhibitor also downregulates angiogenic proteins, such as ANXA2 (43), ANXA4 (44), PRDX6 (45), and PHB (46), and upregulates CPNS1, a protein favoring cell damage and senescence (47).…”

Annexin II interactions with the annexin II receptor enhance multiple myeloma cell adhesion and growth in the bone marrow microenvironment

“…Previous studies report that AXII is up-regulated in MM, 15,16 and that MM-derived AXII increased proliferation of MM cell lines, U266 and RPMI8226, suggesting that in these MM cells, the MM-derived AXII acts in an autocrine manner to support proliferation of the MM cells. However, in our studies, addition of anti-AXII to MM1.S cells did not decrease MM cell growth in the absence of added AXII, even though AXII is expressed by these MM cell lines (supplemental Figure 1).…”

“…15 More recently, AXII was shown to increase the proliferation of, and had antiapoptotic effects on, human MM cell lines. 16 Based on these previous studies, it is our hypothesis that AXII and AXIIR mediate critical interactions between MM cells, stromal cells/OBL, and OCLs in the BM microenvironment that promote MM cell growth. In this study, we show that AXIIR is expressed by MM cell lines and CD138 ϩ cells from MM patients, and that both AXII and AXIIR are involved in adhesion of MM cells to OBL and stromal cells through RhoA.…”