| 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. |
| 人乳脂球上皮生长因子8通过促进血管内皮增生和抑制宿体免疫而促进肿瘤生长 |
| 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 |
| DOI：10.1007/s10330-016-0184-4 |
| 中文关键词: 人乳脂球上皮生长因子8；肿瘤； 靶向治疗； 血管生成； 细胞凋亡 |
| 英文关键词: milk fat globule epithelial growth factor VIII (MFG-E8); carcinoma; target therapy; angiogenesis; apoptosis |
| 基金项目: |
| 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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| 中文摘要: |
| 人乳脂肪球上皮生长因子8主要是由巨噬细胞和树突状细胞产生的粘附蛋白，能在大多数人体组织中表达。它包含用于分泌的信号序列的NH 2末端的两个表皮生长因子（EGF）和在COOH端两个盘状结构域类似凝血因子V /因子VIII（C1和C2）。第二EGF结构域包含精氨酸 - 甘氨酸 - 天冬氨酸（RGD）整联蛋白结合基序，其接合αVβ5整联，以促进细胞粘附和诱导整合素介导的信号转导。整合素αvβ3与VEGF受体2，可以促进血管生成，它在肿瘤细胞的生长，增殖和存活中起关键角色。血管内皮生长因子刺激αvβ3和αVβ5在血管内皮的表达，从而增效VEGF受体的作用。 C-末端盘状样结构结合膜磷脂，使得附近的血管内皮生长因子的血管生成。 MFG-E8为凋亡细胞调理素，并且它作为凋亡细胞和吞噬细胞之间的桥连蛋白。它还通过改变CD4 +和/或CD8 +细胞的影响细胞免疫。抗体及小的多肽于MFG-E8在上EGF样结构域和/或盘状样结构域不同领域结合，可以影响抗血管生成和免疫。改变MFG-E8有希望开发新的抗肿瘤药物。 |
| 英文摘要: |
| 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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