ALCAM (CD166): its role in hematopoietic and endothelial development

Onodera, Osamu; Ohneda, Kinuko; Arai, Fumio; Lee, James; Miyamoto, Takeshi; Fukushima, Yoshio; Dowbenko, Donald; Lasky, Laurence A.; Suda, Toshio

doi:10.1182/blood.v98.7.2134

Cited by 133 publications

(112 citation statements)

References 26 publications

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…The CD6L CD166 is found on the surface of epithelial cells, SFs, activated macrophages, and mesenchymal stem cells (9 -11, 17, 31). CD166 mediates homotypic binding of cells, is strongly expressed in RA synovium and in melanoma metastases, and has recently been reported to play a role in neoangiogenesis (13)(14)(15). We had previously hypothesized that CD6L other than CD166 were expressed on tissue APC (16,32,33).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Expression and Characterization of a Novel CD6 Ligand in Cells Derived from Joint and Epithelial Tissues

Saifullah

Fox

Sarkar

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

CD6 is a T cell surface glycoprotein that plays an important role in interactions of thymocytes with thymic epithelial cells and in mature T cell interactions with selected nonprofessional tissue APCs. We describe a novel CD6 ligand (CD6L) 3A11 Ag that is distinct from the known CD6L (CD166). The 3A11 protein is expressed on cells derived from human thymus, skin, synovium, and cartilage, and its expression is enhanced by IFN-γ. mAbs directed against the 3A11 Ag and CD166 exhibit distinct patterns of binding to a panel of cell lines. Confocal microscopy shows that both CD166 and the 3A11 Ag are expressed at the cell surface, and that these proteins colocalize. The 3A11 Ag has a molecular mass of 130 kDa and is immunoprecipitated using either mAb 3A11 or soluble CD6-Ig fusion protein. mAbs directed against individual CD6L were less potent than was soluble CD6-Ig fusion protein in reducing adhesion of T cells to adherent 3A11-positive epithelial cells in vitro, suggesting that these Abs recognize epitopes on the 3A11 Ag and CD166 that are distinct from CD6 binding sites. Finally, transfection of epithelial cells with CD166-specific small interfering RNAs significantly decreased CD166 expression without alteration in 3A11 Ag levels, and thus confirmed that these two CD6L are distinct. Taken together, our data identifies a novel 130-kDa CD6L that may mediate interactions of synovial and epithelial cells with T lymphocytes.

show abstract

Section: Discussionmentioning

confidence: 99%

“…In vitro, this mAb also reduced binding of thymocytes to thymic epithelial cells and homotypic binding of these epithelial cells (9), implying a role for interactions between CD6 and CD6L in thymocyte development. CD166 has been reported to be important in establishment of hemopoesis (13)(14)(15).…”

mentioning

confidence: 99%

Expression and Characterization of a Novel CD6 Ligand in Cells Derived from Joint and Epithelial Tissues

Saifullah

Fox

Sarkar

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…6 ALCAM is a cell-surface immunoglobulin superfamily member expressed by primitive hematopoietic stem cells and associated with embryonic hematopoiesis as well as vasculogenesis. 7 Interestingly, stellate cells of rat liver display characteristics of stem/ progenitor cells. They express CD133 (cluster designation 133) and Oct4 (octamer 4), which are known from pluripotent stem cells, and can differentiate into hepatocyte-like and endothelial-like cells in vitro.…”

Section: S Tellate Cells Reside Within the Perisinusoidal Space Ofmentioning

confidence: 99%

The niche of stellate cells within rat liver

et al. 2009

View full text Add to dashboard Cite

“…Heterophilic CD6-ALCAM interactions have also been suggested to play a role in the development of hemopoietic stem cells and endothelial progenitors (10,11). Recently a novel, still uncharacterized CD6 ligand has been found expressed on synovial and epithelial cells (12).…”

mentioning

confidence: 99%

Mitogen-Activated Protein Kinase Pathway Activation by the CD6 Lymphocyte Surface Receptor

Ibáñez

Sarrias

Farnós

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

CD6 is a cell surface receptor primarily expressed on immature thymocytes and mature T and B1a lymphocytes. Through its binding to activated leukocyte cell adhesion molecule (ALCAM/CD166), CD6 is considered to play an important role in lymphocyte development and activation. Accordingly, CD6 associates with the TCR/CD3 complex and colocalizes with it at the center of the mature immunological synapse on T lymphocytes. Moreover, the CD6-ALCAM interaction has been shown to be critical for proper immunological synapse maturation and T cell proliferative responses. However, the precise biological effects of CD6 ligation and its signaling pathway are still not well understood. The present study shows that CD6 ligation with three different specific mAbs (161.8, SPV-L14.2, and MAE1-C10) induces time- and dose-dependent activation of ERK1/2 on normal and leukemic human T cells. This effect was also observed upon CD6 ligation with a chimerical ALCAM protein (ALCAM-Fc). The C-terminal cytoplasmic region of CD6, as well as Src tyrosine kinases, was critical for CD6-induced ERK1/2 activation. Synergistic effects were observed upon coligation of the TCR/CD3 complex with CD6. The ligation of CD6 induced the transcriptional activation of reporter genes under the control of the c-Fos serum responsive element and AP-1. Accordingly, CD6-mediated activation of p38 and JNK was also observed. These findings indicate that the CD6-ALCAM interaction results in activation of the three MAPK cascades, likely influencing the dynamic balance that determines whether resting or activated lymphocytes survive or undergo apoptosis.

show abstract

ALCAM (CD166): its role in hematopoietic and endothelial development

Cited by 133 publications

References 26 publications

Expression and Characterization of a Novel CD6 Ligand in Cells Derived from Joint and Epithelial Tissues

Expression and Characterization of a Novel CD6 Ligand in Cells Derived from Joint and Epithelial Tissues

The niche of stellate cells within rat liver

Mitogen-Activated Protein Kinase Pathway Activation by the CD6 Lymphocyte Surface Receptor

Contact Info

Product

Resources

About