HCA, an Immunoglobulin-Like Adhesion Molecule Present on the Earliest Human Hematopoietic Precursor Cells, Is Also Expressed by Stromal Cells in Blood-Forming Tissues

Abstract

We have previously shown that the HCA/ALCAM (CD166) glycoprotein, a member of the immunoglobulin family that mediates both homophilic and heterophilic cell-cell adhesion, via the CD6 ligand, is expressed at the surface of all of the most primitive CD38−/lo, Thy-1+, rho123lo, CD34+hematopoietic cells in human fetal liver and fetal and adult bone marrow. In the present report we show that HCA is also expressed by subsets of stromal cells in the primary hematopoietic sites that sequentially develop in the human embryo and fetus, ie, the paraaortic mesoderm, liver, thymus, and bone marrow. Adult bone marrow stromal cells established in vitro, including those derived from Stro-1+ progenitors and cells from immortalized cell lines, express HCA. In contrast, no HCA expression could be detected in peripheral lymphoid tissues, fetal spleen, and lymph nodes. HCA membrane molecules purified from marrow stromal cells interact with intact marrow stromal cells, CD34+ CD38−hematopoietic precursors, and CD3+ CD6+peripheral blood lymphocytes. Finally, low but significant levels of CD6 are here for the first time detected at the surface of CD34+ rho123med/lo progenitors in the bone marrow and in mobilized blood from healthy individuals. Altogether, these results indicate that the HCA/ALCAM surface molecule is involved in homophilic or heterophilic (with CD6) adhesive interactions between early hematopoietic progenitors and associated stromal cells in primary blood-forming organs.

Alcam Regulates Long-Term Hematopoietic Stem Cell Engraftment and Self-Renewal

“…Notably, ALCAM has been reported to mark a tumor-initiating cell population in prostate cancer and in lung cancer [27,28]. In the hematopoietic system, ALCAM is expressed on activated lymphocytes and monocytes and on primitive human HSCs [29,30]. In addition, Alcam is reportedly required for myeloid colony formation in avian embryonic hematopoietic progenitors [31], and Alcam-expressing endothelial cells can support murine embryonic hematopoiesis [18].…”

miR‐221 redirects precursor B cells to the BM and regulates their residence

“…The upregulation of syndecan-4 is induced by Pax5, as multipotent CLP-like pro-/pre-B cells commit themselves to B-cell differentiation [18,30]. Syndecan-4 is also expressed on stromal cells located in fetal liver and BM in the proximity of these proB and preBCR + pre-B cells [31]. More specifically, syndecan-4 could interact with the non-Ig portion of the lambda5-component of it [32].…”

The liver as a nursery for leukocytes

“…HSC interacts with stromal cells and the extracellular matrix and are retained in fetal liver. 28 This interaction occurs through the expression of VE-cadherin, A2b-intregrin, B1-integrin, c-Kit, and CXCR4 in HSCs, 29 and via CD166 30 and stem cell factor expression in stromal cells. Together, this promotes HSC-cell or HSC-matrix interactions.…”