Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1

Nagasawa, Takashi; Hirota, Seiichi; Tachibana, Kazunobu; Takakura, Nobuyuki; Nishikawa, Shin‐Ichi; Kitamura, Yukihiko; Yoshida, Nobuaki; Kikutani, Hitoshi; Kishimoto, Tadamitsu

doi:10.1038/382635a0

Cited by 2,195 publications

(1,729 citation statements)

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“…Three of five MDS patients and 5/7 AML patients showed a marked migration in response to HGF/SF. Supernatant of BM stromal cells, which contains a strong chemoattractant (SDF-1) for hemopoietic progenitor cells, was superior to HGF/SF in inducing migration 61,62 (Table 4). The chemoattractive property of BM stroma supernatant was partially reversed by the addition of a neutralizing monoclonal antibody directed to HGF/SF, suggesting that HGF/SF, which is present in supernatant of BM stromal cells (approximately 1-2 ng/ml; 27 ), is at least partly responsible for the migration promoting effect.…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte growth factor/scatter factor (HGF/SF) affects proliferation and migration of myeloid leukemic cells

et al. 1998

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Hepatocyte growth factor (HGF), also known as scatter factor (SF), is produced by mesenchymal cells, including bone marrow (BM) stromal cells, and has mitogenic and motogenic effects on a variety of cell types. Recently, a role has been assigned to HGF/SF and its receptor, c-MET, in both normal and malignant hemopoiesis. We investigated the function of HGF/SF on hemopoietic mononuclear cells (MNC) from patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with circulating blasts. In contrast to results with normal MNC, HGF/SF alone stimulated the proliferation and colony formation of MNC from these patients. MNC from some (4/13) of the AML patients also produced HGF/SF (0.1-0.2 ng/ml/day), while we could not detect HGF/SF in cultures from normal MNC. Furthermore, it appeared that HGF/SF induced migration of leukemic cells in Boyden using KG1a cells as a model for leukemic blasts. The membranes dividing the two compartments of the Boyden chambers were coated with fibronectin. HGF/SF significantly promoted migration in 3/5 samples of MDS patients and in 5/7 samples of AML patients. Supernatant of human BM stromal cells, which is chemoattractive for normal human hemopoietic progenitor cells, also promoted migration of MNC from 4/5 MDS patients and 6/7 AML patients. Since HGF/SF is one of the growth factors produced by BM stromal cells, a neutralizing antibody directed against HGF/SF was added to the BM stroma supernatant, which reduced migration significantly in 2/3 MDS and in 3/6 AML responders to BM stroma supernatant. In conclusion, HGF/SF promotes proliferation and migration of hemopoietic cells from AML and MDS patients in vitro and may therefore contribute to the malignant potential of these cells.

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Section: Discussionmentioning

confidence: 99%

Hepatocyte growth factor/scatter factor (HGF/SF) affects proliferation and migration of myeloid leukemic cells

et al. 1998

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“…These include adhesion proteins such as integrins as well as enzymes like the metalloproteinases (MMPs), which support tumor invasion in connective tissue. 4,5 Emerging evidence suggests that a third family, the chemokines and their receptors, are involved in organ-specific metastasis. Chemokines are a superfamily of small, secreted proteins (8 -10 kDa) that function to set up immune and inflammatory reactions.…”

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confidence: 99%

CXCR4 expression reflects tumor progression and regulates motility of bladder cancer cells

Retz

Sidhu

Blaveri

et al. 2004

Intl Journal of Cancer

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Transitional cell carcinoma of the urinary bladder remains life threatening due to the high occurrence of metastases. Emerging evidence suggests that chemokines and their receptors play a critical role in tumor metastases. In our study, we performed a systematic analysis of the mRNA and protein expression levels of all 18 chemokine receptors in normal urothelium and bladder cancer. CXCR4 was the only chemokine receptor whose mRNA expression level was upregulated in bladder cancer cell lines as well as in invasive and locally advanced bladder cancer tissue samples (pT2-pT4). In contrast, superficial bladder tumors (pTa and pT1) displayed low CXCR4 expression levels and normal urothelial cells were negative for CXCR4. Immunohistochemistry of a bladder cancer tissue microarray (TMA) confirmed that a subgroup of invasive bladder cancers revealed a high CXCR4 protein expression, while superficial bladder tumors showed low immunoreactivity. To investigate the functional significance of CXCR4 expression, we performed migration and invasion assays. Exposure of CXCR4-positive bladder cancer cells to CXCL12 in a Boyden chamber type assay provoked a significant increase in migration as well as invasion across a Matrigel barrier. Enhanced migration and invasion were inhibited by a CXCR4-specific blocking antibody. In contrast, normal urothelial cells did not respond to CXCL12 and lacked chemotactic migration. In conclusion, bladder cancer cells express CXCR4 progressively with advanced tumorigenesis and this receptor interacts with CXCL12 to mediate tumor chemotaxis and invasion through connective tissue. These properties identify CXCR4 as a potential target for the attenuation of bladder cancer metastases. © 2004 Wiley-Liss, Inc.Key words: chemokine; bladder cancer; metastasis; migration; invasion Transitional cell carcinoma of the bladder is the most frequent tumor of the urinary tract. Despite advances in early detection and therapy, bladder cancer remains life threatening due to the high occurrence of metastases. Radical cystectomy is the preferred treatment for muscle-invasive bladder cancer in the United States, Japan and some countries of Europe. However, at least 50% of patients with locally advanced disease are expected to develop systemic progression within 3 years. 1 Patients suffering from metastatic bladder cancer are commonly treated with systemic chemotherapy. Analyzing survival rates from standard chemotherapy schedules such as M-VAC (methotrexate, vinblastine, adriamycin and cisplatin), results are more or less discouraging. In the Loehrer trial, only 5 of 133 (3.7%) of the patients randomized to M-VAC were alive at the 6-year follow-up time. These results indicate that patients with systemic metastases continue to be incurable by chemotherapy. 2,3 Despite the fact that it is the metastases rather than the primary tumors that cause most cancer deaths, there has been little progress in identifying drugs to specifically block metastases.Metastasis is not a simple phenomenon, but a highly organized process com...

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“…30 SDF-1 is a chemokine that plays an important role in B-cell development, trafficking, and activation. [8][9][10][11] Several studies suggested that SDF-1 may have a crucial role in the development of autoimmune disease. Matin et al 31 demonstrated that the chemokine SDF-1 may be an essential chemoattractant in trafficking and migration of mature autoreactive B cells from bone marrow to the periphery or inflammatory sites in the development of autoimmune diabetes.…”

Section: Immunohistochemical Stainingmentioning

confidence: 99%

“…7 Stromal cell-derived factor-1 (CXCL12/SDF-1), constitutively expressed in a broad range of tissues, was initially cloned from mouse bone marrow stromal cells and as CXC chemokine originally described as pre-B-cell growthstimulating factor. 8 It is a chemoattractant for monocytes, naive and memory T lymphocytes, and B lymphocytes. [9][10][11] SDF-1 is also a costimulatory factor for CD4 þ T-lymphocyte activation.…”

Section: Introductionmentioning

confidence: 99%

Expression of chemokines and gelatinase B in sympathetic ophthalmia

El-Asrar

Struyf

Broeck³

et al. 2006

Eye

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Purpose To examine the expression of gelatinase B (matrix metalloproteinase-9) and the chemokines monocyte chemotactic protein-1 (CCL2/MCP-1) and stromal cell-derived factor-1 (CXCL12/SDF-1) in sympathetic ophthalmia (SO). Methods Five enucleated exciting eyes with a clinical diagnosis and typical histopathological findings of SO were studied by immunohistochemical techniques using a panel of monoclonal antibodies directed against gelatinase B, MCP-1, and SDF-1. In addition, a panel of monoclonal and polyclonal antibodies was used to characterize the composition of the inflammatory infiltrate. Results In all cases, the extensive uveal inflammatory infiltrate was organized as a diffuse infiltrate and as large granulomas consisting of epithelioid cells and multinucleated giant cells. CD20 þ B lymphocytes predominated in the diffuse infiltrate and CD3 þ T lymphocytes were few. The monocyte/macrophage marker CD68 was expressed in scattered inflammatory mononuclear cells and within granulomas and Dalen-Fuchs nodules. Most of the inflammatory cells were HLA-DR þ . Immunoreactivity for gelatinase B, MCP-1, and SDF-1 was observed in cells within granulomas and in scattered epithelioid cells. Immunoreactivity for MCP-1 was noted in retinal pigment epithelial cells. Endothelial cells of choriocapillaries showed weak immunoreactivity for SDF-1. Conclusions Gelatinase B, MCP-1, and SDF-1 might have a pathogenic role in the recruitment of leucocytes into the eye in SO.

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Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1

Cited by 2,195 publications

References 24 publications

Hepatocyte growth factor/scatter factor (HGF/SF) affects proliferation and migration of myeloid leukemic cells

Hepatocyte growth factor/scatter factor (HGF/SF) affects proliferation and migration of myeloid leukemic cells

CXCR4 expression reflects tumor progression and regulates motility of bladder cancer cells

Expression of chemokines and gelatinase B in sympathetic ophthalmia

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