Stem cell growth factor: in situ hybridization analysis on the gene expression, molecular characterization and in vitro proliferative activity of a recombinant preparation on primitive hematopoietic progenitor cells

Hiraoka, Atsunobu; Yano, Keiichi; Kagami, Naofumi; Takeshige, Kazuhiko; Mio, Hiroyuki; Anazawa, Hideharu; Sugimoto, Seiji

doi:10.1038/sj.thj.6200118

Cited by 49 publications

(53 citation statements)

References 25 publications

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“…4D), which may explain that NK cells conserve high expression of NKR. Moreover, our high content multiplex cytokine/chemokine array analysis on fresh GIST (not shown) confirmed the local secretion of stem cell factor and stem cell growth factor (35,36), which both could contribute to in situ homeostasis or differentiation of NK TILs.…”

Section: Discussionmentioning

confidence: 83%

Immune Infiltrates Are Prognostic Factors in Localized Gastrointestinal Stromal Tumors

et al. 2013

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Cancer immunosurveillance relies on effector/memory tumor-infiltrating CD8þ T cells with a T-helper cell 1(T H 1) profile. Evidence for a natural killer (NK) cell-based control of human malignancies is still largely missing. The KIT tyrosine kinase inhibitor imatinib mesylate markedly prolongs the survival of patients with gastrointestinal stromal tumors (GIST) by direct effects on tumor cells as well as by indirect immunostimulatory effects on T and NK cells. Here, we investigated the prognostic value of tumor-infiltrating lymphocytes (TIL) expressing CD3, Foxp3, or NKp46 (NCR1) in a cohort of patients with localized GIST. We found that CD3 þ TIL were highly activated in GIST and were especially enriched in areas of the tumor that conserve class I MHC expression despite imatinib mesylate treatment. High densities of CD3 þ TIL predicted progression-free survival (PFS) in multivariate analyses. Moreover, GIST were infiltrated by a homogeneous subset of cytokinesecreting CD56 bright (NCAM1) NK cells that accumulated in tumor foci after imatinib mesylate treatment. The density of the NK infiltrate independently predicted PFS and added prognostic information to the Miettinen score, as well as to the KIT mutational status. NK and T lymphocytes preferentially distributed to distinct areas of tumor sections and probably contributed independently to GIST immunosurveillance. These findings encourage the prospective validation of immune biomarkers for optimal risk stratification of patients with GIST. Cancer Res; 73(12); 3499-510. Ó2013 AACR.

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Section: Discussionmentioning

confidence: 83%

Immune Infiltrates Are Prognostic Factors in Localized Gastrointestinal Stromal Tumors

et al. 2013

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“…Previous in vitro studies demonstrated that SCGF promotes enhanced erythroid formation (16). An effective, noninvasive measure of the erythropoietic response, in the absence of bone marrow aspirates, is to determine the reticulocyte production index (RPI), which accounts for the production of erythrocytes corrected for the degree of anemia (24).…”

Section: Resultsmentioning

confidence: 99%

“…Since SCGF promotes growth of erythroid and myeloid colonies (14,16), the associations between SCGF, Hb, and RPI were examined in children with falciparum malaria, both independently and according to SCGF promoter variants. To date, only a single polymorphic variant has been described in the SCGF gene (i.e., Ϫ539C/T).…”

Section: Figmentioning

confidence: 99%

“…Human stem cell growth factor (SCGF) (C-type lectin domain family member 11A [CLEC11A]) is a largely uncharacterized hematopoietic mediator that promotes enhanced erythroid progenitor formation from human bone marrow (16). Human SCGF cDNA encodes a 29-kDa polypeptide (15) for which there are currently two known isoforms: SCGF-␣, a 323-amino-acid protein; and SCGF-␤, a 245-amino-acid protein formed from cleavage of the conserved carbohydrate domain (30).…”

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confidence: 99%

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A Novel Functional Variant in the Stem Cell Growth Factor Promoter Protects against Severe Malarial Anemia

et al. 2010

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Plasmodium falciparum malaria is a leading global cause of infectious disease burden. In areas in which P. falciparum transmission is holoendemic, such as western Kenya, severe malarial anemia (SMA) results in high rates of pediatric morbidity and mortality. Although the pathophysiological basis of SMA is multifactorial, we recently discovered that suppression of unexplored hematopoietic growth factors that promote erythroid and myeloid colony development, such as stem cell growth factor (SCGF) (C-type lectin domain family member 11A [CLEC11A]), was associated with enhanced development of SMA and reduced erythropoietic responses. To extend these investigations, the relationships between a novel SCGF promoter variant (؊539C/T, rs7246355), SMA (hemoglobin [Hb] < 6.0 g/dl), and reduced erythropoietic responses (reticulocyte production index [RPI], <2.0) were investigated with Kenyan children (n ‫؍‬ 486) with falciparum malaria from western Kenya. Circulating SCGF was positively correlated with hemoglobin levels (r ‫؍‬ 0.251; P ‫؍‬ 0.022) and the reticulocyte production index (RPI) (r ‫؍‬ 0.268; P ‫؍‬ 0.025). Children with SMA also had lower SCGF levels than those in the non-SMA group (P ‫؍‬ 0.005). Multivariate logistic regression analyses controlling for covariates demonstrated that individuals with the homologous T allele were protected against SMA (odds ratio, 0.57; 95% confidence interval [95% CI] 0.34 to 0.94; P ‫؍‬ 0.027) relative to CC (wild-type) carriers. Carriers of the TT genotype also had higher SCGF levels in circulation (P ‫؍‬ 0.018) and in peripheral blood mononuclear cell culture supernatants (P ‫؍‬ 0.041), as well as an elevated RPI (P ‫؍‬ 0.005) relative to individuals with the CC genotype. The results presented here demonstrate that homozygous T at ؊539 in the SCGF promoter is associated with elevated SCGF production, enhanced erythropoiesis, and protection against the development of SMA in children with falciparum malaria.

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“…SCGF was shown to be expressed in bone and bone marrow (BM) by whole body in situ hybridization. 3 Although SCGF alone does not exhibit colony-stimulating activity, it does have a burst-promoting activity (BPA) and a granulocyte/macrophage (GM) colony-promoting activity (GPA) on erythroid and GM progenitor cells (BFU-E and CFU-GM) in a primary semisolid clonal culture in combination with erythropoietin (Epo) and GM colony-stimulating factor (GM-CSF), respectively, as well as a CFU-GM-supporting activity during short-term liquid culture of BM cells. However, the significance of SCGF in human hematopoiesis in vivo has not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Serum stem cell growth factor for monitoring hematopoietic recovery following stem cell transplantation

Ito

Sato

Ando

et al. 2003

Bone Marrow Transplant

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Stem cell growth factor: in situ hybridization analysis on the gene expression, molecular characterization and in vitro proliferative activity of a recombinant preparation on primitive hematopoietic progenitor cells

Abstract: SCGF is selectively produced by osseous and hematopoietic stromal cells, and can mediate their proliferative activity on primitive hematopoietic progenitor cells.

Cited by 49 publications

References 25 publications

Immune Infiltrates Are Prognostic Factors in Localized Gastrointestinal Stromal Tumors

Immune Infiltrates Are Prognostic Factors in Localized Gastrointestinal Stromal Tumors

A Novel Functional Variant in the Stem Cell Growth Factor Promoter Protects against Severe Malarial Anemia

Serum stem cell growth factor for monitoring hematopoietic recovery following stem cell transplantation

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