CD38 and CD157: A long journey from activation markers to multifunctional molecules

Abstract

CD38 (also known as T10) was identified in the late 1970s in the course of pioneering work carried out at the Dana-Farber Cancer Center (Boston, MA) that focused on the identification of surface molecules involved in antigen recognition. CD38 was initially found on thymocytes and T lymphocytes, but today we know that the molecule is found throughout the immune system, although its expression levels vary. Because of this, CD38 was considered an ''activation marker,'' a term still popular in routine flow cytometry. This review summarizes the findings obtained from different approaches, which led to CD38 being re-defined as a multifunctional molecule. CD38 and its homologue CD157 (BST-1), contiguous gene duplicates on human chromosome 4 (4p15), are part of a gene family encoding products that modulate the social life of cells by means of bidirectional signals. Both CD38 and CD157 play dual roles as receptors and ectoenzymes, endowed with complex activities related to signaling and cell homeostasis. The structure-function analysis presented here is intended to give clinical scientists and flow cytometrists a background knowledge of these molecules. The link between CD38/CD157 and human diseases will be explored here in the context of chronic lymphocytic leukemia, myeloma and ovarian carcinoma, although other disease associations are also known. Thus CD38 and CD157 have evolved from simple leukocyte activation markers to multifunctional molecules involved in health and disease. Future tasks will be to explore their potential as targets for in vivo therapeutic interventions and as regulators of the immune response. V C 2013 International Clinical Cytometry Society

Binding of CD157 Protein to Fibronectin Regulates Cell Adhesion and Spreading

“…In recent years, we have focused our attention on CD157/BST-1, a glycosylphosphatidylinositol-anchored glycoprotein belonging to the ADP-ribosyl cyclase gene family (3). CD157 is expressed in myeloid, endothelial, and mesothelial cells and in epithelial ovarian cancer cells (4,5). Since its discovery more than 20 years ago, human CD157 (then known as Mo5) (6) has been implicated in the control of leukocyte migration (7).…”

Chimeric antigen receptor T-cell therapies for multiple myeloma

“…71,72 It is normally expressed on precursor B cells, plasma cells, T cells, NK cells, and myeloid precursors. [72][73][74] Among nonhematologic organs, CD38 is expressed on prostate cells, in the nervous system, gut, muscle cells, and on osteoclasts. 72,73 Two monoclonal antibodies against CD38 have been tested clinically, daratumumab and isatuximab.…”

“…[72][73][74] Among nonhematologic organs, CD38 is expressed on prostate cells, in the nervous system, gut, muscle cells, and on osteoclasts. 72,73 Two monoclonal antibodies against CD38 have been tested clinically, daratumumab and isatuximab. 75,76 Used as a single agent, daratumumab had a 36% response rate in patients with refractory myeloma.…”

Contact-dependent Signaling

“…Ligands acting as receptors include ephrins, 45 macrophage colony-stimulating factor (M-CSF), 46 BST1, 40,47 Notch ligands, 48 IL15, 24 neuregulins, 49 semaphorins, 30,50 and members of the TNF superfamily.…”