CD47 update: a multifaceted actor in the tumour microenvironment of potential therapeutic interest

Abstract

CD47 is a ubiquitous 50 kDa five‐spanning membrane receptor that belongs to the immunoglobulin superfamily. This receptor, also known as integrin‐associated protein, mediates cell‐to‐cell communication by ligation to transmembrane signal‐regulatory proteins SIRPα and SIRPγ and interacts with integrins. CD47 is also implicated in cell‐extracellular matrix interactions via ligation with thrombospondins. Furthermore, CD47 is involved in many and diverse cellular processes, including apoptosis, proliferation, adhesion and migration. It also plays a key role in many immune and cardiovascular responses. Thus, this multifaceted receptor might be a central actor in the tumour microenvironment. Solid tumours are composed of not only cancer cells that actively proliferate but also other cell types including immune cells and fibroblasts that make up the tumour microenvironment. Tumour cell proliferation is strongly sustained by continuous sprouting of new vessels, which also represents a gate for metastasis. Moreover, infiltration of inflammatory cells is observed in most neoplasms. Much evidence has accumulated indicating that infiltrating leukocytes promote cancer progression. Given its ubiquitous expression on all the different cell types that compose the tumour microenvironment, targeting CD47 could represent an original therapeutic strategy in the field of oncology. We present a current overview of the biological effects associated with CD47 on cancer cells and stromal cells.

Identification and targeting leukemia stem cells: The path to the cure for acute myeloid leukemia

“…CD47 (also known as Integrin-associated protein, IAP) is one of the unique member of the Ig superfamily, consisting of a V-type Ig-like extracellular domain at its N-terminus, five hydrophobic membrane-spanning segments and a variably spliced (3-36 amino acids) cytoplasmic tail at its C-terminus [40] . CD47 is a receptor for the C-terminal cell binding domain of thrombospondin-1 (TSP-1) and a ligand for the extracellular region of signal-regulatory protein alpha (SIRPα) [41] .…”

“…CD47 is a receptor for the C-terminal cell binding domain of thrombospondin-1 (TSP-1) and a ligand for the extracellular region of signal-regulatory protein alpha (SIRPα) [41] . CD47 is ubiquitously expressed on human cells and involved in many fundamental cellular processes including immune and angiogenic responses [40] . Majeti and co-workers first discovered higher expression of CD47 on AML LSC compared to their normal counterparts, HSC and multipotent progenitor cells (MPP), by flow cytometer and microarray gene expression analysis [42,43] .…”

Mithramycin-loaded mPEG-PLGA nanoparticles exert potent antitumor efficacy against pancreatic carcinoma

“…32,39 Furthermore, the decreased level of CD47 may change tumor microenvironment via interaction with thrombospondin-1 (TSP-1), which is overexpressed in the tumor stroma and takes part in the regulation of angiogenesis and inflammation. 40 Therefore, CD47 inhibition could be an effective treatment strategy for a variety of cancers. The present study suggests that MIT-NPs might be highly effective in CD47 targeting therapy.…”

CD47 expression in cryopreserved equine cutaneous masses and normal skin

“…3,7,24 There are many reported actions of CD47 and its binding partners, including inhibition of phagocytosis, proinflammatory effects, and cell spreading and migration effects. 19,20 When activated, CD47 can induce caspase-independent cell death (type-III programmed cell death). 20 Interruption of the interaction of CD47 and SIRPα could therefore be useful in malignant diseases.…”

“…19,20 When activated, CD47 can induce caspase-independent cell death (type-III programmed cell death). 20 Interruption of the interaction of CD47 and SIRPα could therefore be useful in malignant diseases. In fact, anti-CD47 antibodies have been used in vitro and in vivo to inhibit growth and prevent the spread of tumors.…”