| Keke Nie,Shichao Liu,Youxin Ji,Ling Zhang,Zhongfa Zhang,Xiao Zou. Milk fat globule epithelial growth factor VIII (MFG-E8) sustains survival of cancer cells by prompting tumor angiogenesis and suppressing host immunities. Oncol Transl Med, 2017, 3: 31-37. |
| Milk fat globule epithelial growth factor VIII (MFG-E8) sustains survival of cancer cells by prompting tumor angiogenesis and suppressing host immunities |
| Received:August 17, 2016 Revised:January 23, 2017 |
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| KeyWord:milk fat globule epithelial growth factor VIII (MFG-E8); carcinoma; target therapy; angiogenesis; apoptosis |
| Author Name | Affiliation | Department | | Keke Nie | Oncology Department, Qingdao Cancer Hospital, Qingdao 266042, China | Oncology Department | | Shichao Liu | Oncology Department, Qingdao Cancer Hospital, Qingdao 266042, China | Oncology Department | | Youxin Ji | Oncology Department, Qingdao Central Hospital, The 2nd Affiliated Hospital of Qingdao University, Qingdao 266042, China | Oncology Department | | Ling Zhang | Oncology Department, Qingdao Cancer Hospital, Qingdao 266042, China | Oncology Department | | Zhongfa Zhang | Oncology Department, Qingdao Cancer Hospital, Qingdao 266042, China | Oncology Department | | Xiao Zou | Oncology Department, Qingdao Central Hospital, The 2nd Affiliated Hospital of Qingdao University, Qingdao 266042, China | Oncology Department |
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| Abstract: |
| Milk fat globule epithelial growth factor VIII (MFG-E8) is a novel adhesion protein mainly produced by
macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt
cancer progression and survival. MFG-E8 contains a signal sequence for secretion, two epidermal growth
factor (EGF)-like domains at the NH2 terminus and two discoidin domains with blood-clotting factor V/factor
VIII (C1 and C2) at the COOH terminus. The second EGF domain contains an arginine-glycine-aspartic
(RGD) integrin-binding motif that engages avb5 integrins to facilitate cell adhesion and induce integrinmediated
signal transduction. Integrin avb3 associates with VEGF receptor 2, engagement of integrins can
promote angiogenesis, which plays key roles in growth, proliferation, and survival of cancer cells. VEGF
stimulates the expression of avb3 and avb5 integrins on angiogenic vasculature, thereby potentiating effects
of VEGF receptor engagement. Mice expressing a mutant form of avb3 integrin are unable to undergo
tyrosine phosphorylation, confirming the important role that this integrin plays in pathological angiogenesis
and providing important mechanistic insights. The C-terminus discoidin-like domains promote binding to
membrane phospholipids, functioning close to VEGF like angiogenesis. MFG-E8 is an opsonin for apoptotic
cells, and it acts as a bridging protein between apoptotic cells and phagocytes. It also influences cell
immunities by altering CD4 and/or CD8 cells. Antibody or small peptide works with MFG-E8 at different
functional sites or interacts with EGF-like domains and/or discoidin-like domains may play an important role
in anti-angiogenesis or immune restoration. Altering the structures and/or functions of MFG-E8 and/or its
domains is promising for development of novel anti-cancer strategies. |
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