Identification of a cell-surface antigen associated with activated T lymphoblasts and activated platelets

Sutherland, D. Robert; Yeo, Erik; Ryan, Anne; Mills, G; Bailey, Denis; Baker, Michael A.

doi:10.1182/blood.v77.1.84.bloodjournal77184

Cited by 49 publications

(73 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These contradictory results are either explained by the use of different CD109 mAbs or by differences in platelet preparation and buffers used. The mAbs 1B3 and 8A3 do not react with resting platelets but, in both cases, platelets were obtained by gel filtration in the presence of inhibitors of activation such as prostaglandin I 2 and acetylsalicylic acid (Sutherland et al, 1991;Bordin et al, 1997). Previous studies with mAb D2 showed binding to platelets obtained from standard platelet concentrates (Haregewoin et al, 1994), and this is confirmed in the current study.…”

Section: Discussionsupporting

confidence: 85%

Detection of Gov system antibodies by MAIPA reveals an immunogenicity similar to the HPA‐5 alloantigens

Berry

Murphy²,

Smith³

et al. 2000

Br J Haematol

107

View full text Add to dashboard Cite

Summary. The glycosylphosphatidylinositol-linked platelet protein CD109 carries the biallelic alloantigen system Gov. There is limited information on the incidence of Gov alloantibodies in neonatal alloimmune thrombocytopenia (NAITP), post-transfusion purpura (PTP) and platelet refractoriness. We adapted the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay to the detection of Gov antibodies and determined their incidence in 605 archived samples (112 with HPA antibodies) referred for the aforementioned conditions. Here, we show that CD109 expression was reduced upon platelet storage in saline or by cryopreservation, but was stable when stored as whole blood or therapeutic platelet concentrate. Fourteen of the 605 samples contained Gov alloantibodies (anti-Gov a , n 10; anti-Gov b , n 4), with the majority in platelet refractoriness (n 9) and, of the remaining five, four in NAITP and one in PTP. In seven cases, no other HPA antibodies were detected, three being NAITP cases. The incidence of Gov antibodies was significantly lower than HPA-1 system antibodies (n 87), but equalled the number of HPA-5 system antibodies (n 14) and outnumbered HPA-2 and -3 system antibodies (10 altogether).

show abstract

Section: Discussionsupporting

confidence: 85%

Detection of Gov system antibodies by MAIPA reveals an immunogenicity similar to the HPA‐5 alloantigens

Berry

Murphy²,

Smith³

et al. 2000

Br J Haematol

107

View full text Add to dashboard Cite

show abstract

“…(15) CD109-positive immunoreactivity in normal tissues was also detected in restricted cells, such as myoepithelial cells of the mammary, salivary and lacrimal glands, and basal cells of the prostate. (16) Our findings, together with previous reports showing CD109 expression on hematopoietic and mesenchymal stem cell subsets, activated T lymphoblasts and platelets, and some human tumor cell lines, (1,2,4,5) demonstrate that CD109 plays a role in cell proliferation and tumor development, especially that of SCC, and that CD109 expression in normal tissues may be strictly controlled. In the present study, we assessed the significance of CD109 expression in tumor development and cell proliferation using human oral tumor tissues and cancer cell lines.…”

Section: Discussionsupporting

confidence: 79%

Up‐regulation of CD109 expression is associated with carcinogenesis of the squamous epithelium of the oral cavity

Hagiwara

Murakumo²,

Sato³

et al. 2008

Cancer Science

View full text Add to dashboard Cite

CD109 is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein whose expression is up-regulated in squamous cell carcinomas (SCCs) of the lung, esophagus, and uterus. The purpose of this study was to evaluate CD109 expression in oral tumors, including premalignant lesions, and to assess the clinical application of CD109 in oral cancer. CD109 expression in oral normal and tumor tissues from 124 patients was examined by immunohistochemical staining with anti-CD109 antibody, and significant relations between clinical features and CD109 expression were statistically assessed. We found that high levels of CD109 expression were frequently detected in SCCs and premalignant lesions of the oral cavity, but not in normal squamous epithelia. The CD109 expression level was higher in well-differentiated SCCs than in poorly differentiated SCCs. Furthermore, premalignant lesions highly expressing CD109 showed higher risk to progress to SCCs. Oral SCC cell lines overexpressing CD109 exhibited accelerated cell growth in vitro compared with control cell lines. In addition, overexpression of CD109 impaired the transforming growth factor (TGF)-b1-mediated suppression of cell growth. These findings suggest that CD109 plays a role in the development of oral cancers, and is a useful prognostic marker to predict malignant transformation of premalignant lesions. (Cancer Sci 2008; 99: 1916-1923 U p-regulation or down-regulation of the expression of some genes, including oncogenes and tumor suppressor genes, trigger the development of human tumors; the products of these genes are potentially good molecular targets for cancer diagnosis and treatment. In oral cancers, despite the ease of clinical examination, most cancer patients are diagnosed with advanced-stage cancer and are difficult to treat because of the anatomic location of the lesions or because the treatment would impact on the patients' quality of life. Therefore, early diagnosis of high-risk premalignant lesions is most important for good prognosis.CD109 is a glycosylphosphatidylinositol (GPI)-anchored cellsurface glycoprotein and is a member of the α2-macroglobulin-C3, C4, and C5 family of thioester-containing proteins.(1-3) The CD109 protein was first identified as a cell-surface antigen detected by a monoclonal antibody raised against the primitive lymphoid/ myeloid cell line KG1a.(1) It has been reported that CD109 is expressed on a subset of fetal and adult CD34 + bone marrow mononuclear cells, mesenchymal stem cell subsets, phytohemagglutinin (PHA)-activated T lymphoblasts, thrombin-activated platelets, leukemic megakaryoblasts, endothelial cells, and some human tumor cell lines, but not on fresh peripheral leukocytes and normal bone marrow leukocytes.(1,2,4,5) It was also shown that CD109 carries the biallelic platelet-specific alloantigen Gov, which is implicated in refractoriness to platelet transfusion, post-transfusion purpura, and neonatal alloimmune thrombocytopenia. We identified CD109 as a gene up-regulated in cells overexpressing oncogenic RET tyrosine kinas...

show abstract

“…Although CD109 has been shown to be an activation antigen for T cells and platelets (24), to carry the platelet Gov alloantigen system (27), and to be expressed widely in human tissues (29), the physiological function of this protein is not known. Results from the present study linking CD109 function to regulation of TGF-␤1 signaling in vitro suggest that it may play a similar role in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…CD109 is a GPI-anchored protein, first identified using monoclonal antibodies raised against the human leukemia cell line KG1a, on activated T cells and platelets and on a subset of hematopoetic progenitor cells (23,24), with a wider distribution reported more recently (25,26). Although CD109 has been found to represent the Gov alloantigen on platelets (27), and its molecular cloning as a novel member of the ␣2macroglobulin(␣2M)/complement gene family has recently been reported (28,29), its function has remained unknown.…”

mentioning

confidence: 99%

Identification of CD109 as part of the TGF‐β receptor system in human keratinocytes

et al. 2006

View full text Add to dashboard Cite

We have previously reported that keratinocytes defective in glycosylphosphatidylinositol (GPI)-anchor biosynthesis display enhanced TGF-beta responses. These studies implicated the involvement of a 150 kDa GPI-anchored TGF-beta1 binding protein, r150, in modulating TGF-beta signaling. Here, we sought to determine the molecular identity of r150 by affinity purification and microsequencing. Our results identify r150 as CD109, a novel member of the alpha2-macroglobulin (alpha2M)/complement superfamily, whose function has remained obscure. In addition, we have identified a novel CD109 isoform that occurs in the human placenta but not keratinocytes. Biochemical studies show that r150 contains an internal thioester bond, a defining feature of the alpha2M/complement family. Loss and gain of function studies demonstrate that CD109 is a component of the TGF-beta receptor system, and a negative modulator of TGF-beta responses in keratinocytes, as implicated for r150. Our data suggest that CD109 can inhibit TGF-beta signaling independently of ligand sequestration and may exert its effect on TGF-beta signaling by direct modulation of receptor activity. Together, our results linking CD109 function to regulation of TGF-beta signaling suggest that CD109 plays a unique role in the regulation of isoform-specific TGF-beta signaling in keratinocytes.

show abstract

Identification of a cell-surface antigen associated with activated T lymphoblasts and activated platelets

Cited by 49 publications

References 25 publications

Detection of Gov system antibodies by MAIPA reveals an immunogenicity similar to the HPA‐5 alloantigens

Detection of Gov system antibodies by MAIPA reveals an immunogenicity similar to the HPA‐5 alloantigens

Up‐regulation of CD109 expression is associated with carcinogenesis of the squamous epithelium of the oral cavity

Identification of CD109 as part of the TGF‐β receptor system in human keratinocytes

Contact Info

Product

Resources

About