Table 1 Roles of Del-1 in disease and pathophysiological conditions

Pro-oncogene s roles

Liver cancer

Plays an important role in the process of tumor cells moving from the primary site

The expression of Del-1 was higher in the human liver hepatocellular carcinoma cell line, tumor cell-EC adhesion was inhibited by antibodies against αvβ3, αvβ5

Niu et al. [26]

Breast cancer

A biomarker and a progression predictor

Del-1 are upregulated both in plasma and circulating extracellular vesicles of early-stage breast cancer patients, the sensitivity of Del-1 for early-stage breast cancer diagnosis is higher than in CA-153; Del-1 is correlated with cancer progression and worse survival trend in triple-negative breast cancer

Moon et al. [27], Lee et al. [28]

Liver cancer

A poor prognosis predictor

EDIL3 was highly expressed in the HCC patients, Multivariate Cox’s analysis showed that the EDIL3 expression level was a significant and independent prognostic parameter for the overall survival rate of HCC patients

Sun et al. [31]

Liver cancer

Enhancing the tumorigenic, metastatic, and angiogenesis potential

Overexpression of EDIL3, which was regulated by the downregulation of miR-137 in HCC, triggered the activation of ERK and TGF-β signaling through interactions with αvβ3 integrin. Blocking ERK and TGF-β signaling overcomes EDIL3 induced angiogenesis and invasion

Xia et al. [32]

Bone marrow niche

Promoting the proliferation and differentiation of HSCs into myeloid lineage

In the bone marrow niche, Del-1 binds to HSCs αvβ3 integrin on one end and interacts with the extracellular matrix on the other end, thus promoting HSCs proliferation and differentiation into the myeloid lineage

Mitroulis et al. [21], Chen et al.

Anti-inflammatory roles

Inflammation

Exerting anti-inflammatory effects by inhibiting neutrophil recruitment and migration

In the vessel lumen, endothelial cell-derived Del-1 blocks the binding of αLβ2(LFA-1) integrin on neutrophils to ICAM-1 on vascular endothelial cells, thereby blocking the adhesion and migration of neutrophils

Vestweber et al. [16]

Inflammation resolution

Accelerating macrophage efferocytosis and inflammation resolution

In the course of the resolution of inflammation, Del-1 connects PS on apoptotic cells at one end to αvβ3 integrin on macrophages at the other end as a bridge of cell-to-cell communication and the uptake of apoptotic cells by macrophages. Del-1 makes the hepatic X receptor-related pathway reprogram macrophages, which transform macrophages into the pro-resolving phenotype

Kourtzelis et al. [9]

Periodontitis

Inhibits osteoclastogenesis and protects against inflammatory bone loss

Del-1 inhibited the expression of NFATc1 in a Mac-1 integrin-dependent manner in periodontitis. Del-1 regulated mouse osteoclast differentiation and function, RGD motif, and E1–E3 repeats of Del-1 involved in osteoclast formation and function. Del-1 also protected against inflammatory bone loss in periodontitis mice which Del-1-Fc was a crucial component of

Shin et al. [50]