Mobilization of Myeloma Cells Involves SDF‐1/CXCR4 Signaling and Downregulation of VLA‐4

Gazitt, Yair; Akay, Cagla

doi:10.1634/stemcells.22-1-65

Cited by 58 publications

(50 citation statements)

References 62 publications

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“…Then, such frequency is far from those of the French and of the Spanish population (0.329 and 0.359) and more closer to our result in Tunisian population [Yair Gazitt & Cagla Akai, 2004].…”

Section: Discussionsupporting

confidence: 83%

Distribution of SDF1-3’A, GNB3 C825T and MMP-9 C-1562T Polymorphisms in HSC CD34+ from Peripheral Blood of Patients with Hematological Malignancies

Moufida¹,

Jenhani²

2012

Advances in Hematopoietic Stem Cell Research

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“…Then, such frequency is far from those of the French and of the Spanish population (0.329 and 0.359) and more closer to our result in Tunisian population [Yair Gazitt & Cagla Akai, 2004].…”

Section: Discussionsupporting

confidence: 83%

Distribution of SDF1-3’A, GNB3 C825T and MMP-9 C-1562T Polymorphisms in HSC CD34+ from Peripheral Blood of Patients with Hematological Malignancies

Moufida¹,

Jenhani²

2012

Advances in Hematopoietic Stem Cell Research

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“…This function of SDF-1/CXCR4 axis has been confirmed in several tumors such as lung cancer, prostate carcinoma and breast cancer. 14,15,17,[43][44][45][46][47][48][49][50][51] Our previous report found that the CXCR4 expression in NPC lesions was positively correlated with tumor distant metastasis and poor survive. 52 In this study, in 56 NPC lesions 30% (17/56) had a high expression level of CXCR4, and the CXCR4 was expressed in the cellular nucleus or cytoplasm and membrane of NPC tumor cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies suggested that the SDF-1/CXCR4 axis play an important and unique role not only in the egress of haematopoietic stem/progenitor cells from bone marrow into peripheral blood during mobilization and organogenesis, but also for tumor metastasis and development. [14][15][16][17][18][19][20] It is becoming clear, however, that neoplastic cells might evade the adaptive immune system by altering the expressions of specific molecules on the target cells. MHC class I is responsible for direct presentation of tumor antigen peptides to cytotoxic T lymphocytes (CTLs) ( via peptide-MHC complexes, while HLA class II can endogenously derive peptides to CD4+ T cells.…”

mentioning

confidence: 99%

Expression of immune-related molecules in primary EBV positive chinese nasopharyngeal carcinoma: Associated with latent membrane protein 1 (LMP1) expression

Li¹,

Zhang²,

Xie³

et al. 2007

Cancer Biology & Therapy

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To understand the role of Epstein-Barr virus (EBV) and viral products in associated with immunophenotype and clinical outcome of primary nasopharyngeal carcinoma (NPC), the expression levels of chemokines IFN-g-induced protein 10 (IP-10, CXCL10), stromal-derived factor-1 (SDF-1, CXCL12) and its receptor CXCR4 was investigated in 56 primary NPC biopsy specimens from Chinese NPC patients in parallels with LMP1 antigen and EBER1 by immunohistochemisty (IHC) and in situ hybridization (ISH). Moreover, the expression levels of HLA class I (b-microglobulin) and II antigen (HLA-DR), and co-stimulatory molecule CD54 were also evaluated in 31 out of these 56 patients using immunohistochemisty (IHC). Our results showed that (a) the elevated expression levels of IP10, SDF-1, CXCR4, b-microglobulin, HLA-DR and CD54 in NPC lesions was 66%, 36%, 30%, 42%, 55% and 69%, respectively. The differentiated nonkeratinizing and undifferentiated types of nasopharyngeal carcinoma (NPC) are associated with Epstein-Barr virus (EBV) in South China, which has the highest incidence rate in the world. 1 The EBV latent type II antigens include nuclear antigen 1 (EBNA1), and latent membrane protein 1 (LMP1, in approximately 50%, seen in ref.2) and protein 2 (LMP2), in addition small non-polyadenylated viral RNAs non-coding nuclear RNAs (EBERs) and BamHI-A rightward transcripts (BARTs) expressed in NPC tumor cells. The expressions of EBV antigens in NPC tumor cells provide the targets for adoptive immunotherapy. [3][4][5][6] However, the poorly differentiated NPC is always characterized by the presence of a highly cellular lymphoid stroma admixed with tumor cells. 7 However, the role of local immunity surrounding NPC cells and the role EBV and viral products expressed in tumor cell remain unclear, which is associated with the expression of immune-related molecules including chemokines and receptors, HLA class I and II antigens, and co-stimulatory molecules and the role of EBV and viral products to alter the expression of immune-related molecules on tumor cells. It has been reported that the expression pattern of immune related-molecules on tumor cells will affect the outcome of T-cell-based adoptive immunotherapy for NPC. [8][9][10] In the tumor bed, chemokines and cytokines are secreted by both tumor-infiltrating immune cells and the tumor cells, and these chemokines and cytokines are capable of pleiotropic effects. 8 For example, IP-10 is a CXC chemokine produced by endothelial cells and macrophages post-stimulated by IFNg. IP-10 can induce rapid and transient adhesion of human IL-2-stimulated T lymphocytes to endothelial cells through its receptor CXCR3, which is selectively expressed on activated T cells. It is thought that expression of IP-10 in tumor cells induces potent anti-tumor functions, such as induction of the Th1 immune response and inhibition of angiogenesis. 11-13 SDF-1 is a a-chemokine, and bind to the only receptor CXCR4. Recent studies suggested that the SDF-1/CXCR4 axis play an important and unique role not only in th...

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“…These actions include the mobilization and adhesion of multiple myeloma plasma cells to stroma (11), the proliferation and migration of multiple myeloma plasma cells (12), the recruitment of osteoclasts to the bone marrow (13), and, most recently, the enhancement of osteoclastic bone resorption (14,15). In this study, we determined whether multiple myeloma plasma cell -derived SDF-1a could stimulate angiogenesis in vitro and examined whether SDF-1a promotes angiogenesis in multiple myeloma patients.…”

mentioning

confidence: 99%

Tumor Angiogenesis Is Associated with Plasma Levels of Stromal-Derived Factor-1α in Patients with Multiple Myeloma

Martin

Dewar

Farrugia

et al. 2006

Clinical Cancer Research

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Purpose: Multiple myeloma is an incurable hematologic malignancy characterized by increased bone marrow angiogenesis and extensive lytic bone disease. We have previously shown that elevated levels of stromal-derived factor-1a (SDF-1a) in peripheral blood plasma are associated with osteolysis in multiple myeloma patients.We have now examined whether SDF-1a levels also correlate with angiogenesis. Experimental Design: We examined the contribution of multiple myeloma plasma cell^derived SDF-1a in the stimulation of in vitro angiogenesis using a tube formation assay. We also collected trephine and peripheral blood plasma samples from patients with multiple myeloma to analyze microvessel density and SDF-1a levels, respectively. Results: We show that multiple myeloma plasma cell line^derived conditioned medium containing SDF-1a stimulates in vitro angiogenesis. In addition, in a large cohort of patients with multiple myeloma and its precursor condition monoclonal gammopathy of undetermined significance, we confirm previous findings that plasma cell burden correlates with both angiogenesis and plasma levels of SDF-1a. We now extend these observations and show the novel finding that peripheral blood plasma levels of SDF-1a positively correlate with the degree of bone marrow angiogenesis in multiple myeloma and monoclonal gammopathy of undetermined significance patients. Conclusions: High levels of SDF-1a produced by multiple myeloma plasma cells promote osteolysis and bone marrow angiogenesis. Therefore, we propose that inhibition of SDF-1a may be an effective mechanism by which angiogenesis and osteolysis can be reduced in multiple myeloma patients.Angiogenesis, or the process of blood vessel formation from preexisting vasculature, plays an important role in the pathology of multiple myeloma in a manner similar to that observed in solid tumors (1). In particular, it has been shown that bone marrow microvessel density (MVD), a surrogate marker of angiogenesis, is elevated in patients with active multiple myeloma compared with those in remission or those with monoclonal gammopathy of undetermined significance (MGUS), a clinical precursor to multiple myeloma (2, 3). Importantly, increased bone marrow MVD is associated with a decreased overall survival in multiple myeloma patients (4 -6).Although the precise molecular mechanisms underlying the progressive increase in angiogenesis in multiple myeloma remain unclear, a number of multiple myeloma plasma cellderived angiogenic growth factors, cytokines, and chemokines have been implicated (7,8). In particular, the chemokine stromal-derived factor-1a (SDF-1a; also known as CXCL12) has recently been shown to stimulate physiologic angiogenesis (9, 10). However, a role for SDF-1a in pathologic angiogenesis, as seen in multiple myeloma, has not been established.SDF-1a, expressed by bone marrow stroma, vascular endothelial cells, and multiple myeloma plasma cells, is involved in many aspects of multiple myeloma biology through interactions with its G-protein -coupled recept...

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Mobilization of Myeloma Cells Involves SDF‐1/CXCR4 Signaling and Downregulation of VLA‐4

Cited by 58 publications

References 62 publications

Distribution of SDF1-3’A, GNB3 C825T and MMP-9 C-1562T Polymorphisms in HSC CD34+ from Peripheral Blood of Patients with Hematological Malignancies

Distribution of SDF1-3’A, GNB3 C825T and MMP-9 C-1562T Polymorphisms in HSC CD34+ from Peripheral Blood of Patients with Hematological Malignancies

Expression of immune-related molecules in primary EBV positive chinese nasopharyngeal carcinoma: Associated with latent membrane protein 1 (LMP1) expression

Tumor Angiogenesis Is Associated with Plasma Levels of Stromal-Derived Factor-1α in Patients with Multiple Myeloma

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