Disease relevance of MFGE8

• Human milk fat globule (HMFG) glycoproteins can prevent infections by microorganisms in breast-fed infants; the MUC-1 mucin inhibits binding of S-fimbriated Escherichia coli to buccal mucosa, and lactadherin may prevent symptomatic rotavirus infections [1].
• Defective release of the epidermal growth factor domain containing a surface RGD motif may be related to involvement of BA46 in breast cancer [2].
• Lactadherin (formerly BA46), a membrane-associated glycoprotein expressed in human milk and breast carcinomas, promotes Arg-Gly-Asp (RGD)-dependent cell adhesion [3].
• BCP8 was similar in tissue reactivity (by immunoperoxidase staining) to anti-breast cancer or anti-human milk fat globule membranes (HMFG) antibodies and reacted strongly with most breast cancers and a proportion of other adenocarcinomas, whether formalin fixed or fresh, and reacted less strongly with some normal tissues [4].
• By contrast, mice immunized with the MUC1 synthetic peptide, a fusion protein, or HMFG have good antibody responses, a delayed-type hypersensitivity reaction, but no cytotoxic T-cells and less tumor protection, possibly a TH2 type response [5].

Psychiatry related information on MFGE8

• In the deep cortical layers of BA 46, Nurr1 mRNA was significantly (P<0.05) lower in patients with bipolar disorder and schizophrenia than in the controls [6].
• Comparing long- and short-term memory tasks yielded activation throughout the frontal cortex, including BA46 [7].

High impact information on MFGE8

• We found that milk fat globule-EGF-factor 8 (MFG-E8), a secreted glycoprotein, was produced by thioglycollate-elicited macrophages [8].
• The NIH3T3 cell transformants that expressed a high level of alpha(v)beta(3) integrin were found to engulf apoptotic cells when MFG-E8 was added [8].
• MFG-E8 specifically bound to apoptotic cells by recognizing aminophospholipids such as phosphatidylserine [8].
• These results indicate that MFG-E8 secreted from activated macrophages binds to apoptotic cells, and brings them to phagocytes for engulfment [8].
• MFG-E8 carrying a point mutation in the RGD motif behaved as a dominant-negative form, and inhibited the phagocytosis of apoptotic cells by peritoneal macrophages in vitro and in vivo [8].

Chemical compound and disease context of MFGE8

• In addition, pretreatment of HMFG with Vibrio cholerae neuraminidase markedly reduced bacterium-induced agglutinations, indicating the involvement of neuraminic acid-containing glycoproteins [9].
• A group of carcinomas were cultured with and without insulin and/or hydrocortisone and the site of staining for milk fat globule membrane, as detected by the antibodies HMFG 1, HMFG 2, and NCRC 11, was assessed using light microscopic and electron microscopic immunohistochemistry [10].
• However, the molecules exclusively reacting with anti-HMFG III D 5, a monoclonal antibody previously shown to detect antigen(s) positively correlating with the expression of estrogen receptors in mammary and gynaecological carcinomas, could only be stained with peanut agglutinin and Ricinus communis-lectins [11].
• From other patients with malignant tumours 2/14 (14%) with endometrial carcinoma, 0/5 with cervical carcinoma, 0/5 with vulvar carcinoma, 1/33 with gastro-intestinal carcinoma, 0/4 with oesophageal carcinoma and 2/45 of patients with leukemia or lymphoma had an elevated serum HMFG value [12].
• HMFG expression was not observed in eight out of nine cases of median raphe cyst of the penis, and the remaining case showed a faint expression of HMFG focally in its luminal surface, while conventional apocrine cystadenoma in extra-genital area expressed HMFG definitively in our previous study [13].

Biological context of MFGE8

• In this study, the survival of these HMFG glycoproteins in the stomach of human milk-fed preterm infants (gestational age = 27.5 +/- 0.4 wk) was assessed, and levels in their mothers' milk determined, using specific RIAs [1].
• Mapping of a newly discovered human gene homologous to the apoptosis associated-murine mammary protein, MFG-E8, to chromosome 15q25 [14].
• Like many anti-mucin antibodies BCP8 reacted with HMFG, but more strongly with deglycosylated HMFG; analysis with peptides by enzyme-linked immunosorbent assay indicated reactivity with an epitope contained in the amino acid motif PDTR and using the pepscan method, the minimum epitope was DTR [4].
• Our data suggest that HMFG inhibit bacterial adhesion in the entire intestine and thereby may provide protection against bacterial infection [9].
• By immunising with HMFG and testing selectively on (a) extracellular (non-VNTR); (b) VNTR and (c) intracellular peptides, it was shown that all three regions generated effective CTL [15].

Anatomical context of MFGE8

• On the microarray these transcripts were up-regulated 7.5-fold for PAI-1 and 4.9-fold for MFGE8 in pregnant myometrium, and down-regulated 3.7-fold for sFRP4 and 2.9-fold for ERalpha in pregnancy [16].
• These results demonstrate that two HMFG glycoproteins implicated in prevention of infection, MUC-1 mucin and lactadherin, survive and maintain their integrity in the stomachs of human milk-fed preterm infants [1].
• Isolation and characterization of full and truncated forms of human breast carcinoma protein BA46 from human milk fat globule membranes [2].
• HMFG inhibited E. coli adhesion to buccal epithelial cells [9].
• Here, the expression of the mammary epithelium related antigens BA46 (lactadherin) and BA70 in lymphoid and myeloid cell lines, and in clinical specimens is analysed [17].

Associations of MFGE8 with chemical compounds

• The two antigens, which are major components of the human milk fat globule membrane, are breast mucin and a M(r) 46,000 glycoprotein (BA46) [18].
• We then sought to boost this response with MUC1-containing synthetic peptides, fusion proteins, and natural mucin (HMFG) [5].
• The BA46 glycoprotein is a breast tumor-associated membrane antigen containing an NH2-terminal, epidermal growth factor-like domain into which a cell adhesion sequence (RGD) is inserted and a COOH-terminal domain with homology to the phospholipid binding C1/C2 domain of coagulation factors V and VIII [18].
• Epithelial Membrane Antigen (EMA), Human Milk Fat Globule II (HMFG II), Estrogen and Progesterone receptors have been detected in adluminal epithelial cells exclusively [19].
• PAS-0 was shown to be resistant to pepsin, trypsin and chymotrypsin digestion, but susceptible to Pronase and Subtilisin BPN'. Extraction of intact milk fat globules (cream) with MgCl2 and guanidine hydrochloride solutions suggested that PAS-0 was an intrinsic component of MFGM [20].

Other interactions of MFGE8

• This antibody exhibited no cross reactions with proteins such as bovine serum albumin, keyhole limpet homocyanin, human serum albumin, casein, human milk fat globin (HMFG), and peptone [21].
• In BA 46, MR mRNA was not significantly different among groups, but was positively correlated with brain pH [22].
• The second gene is milk fat globule epidermal growth factor (EGF) factor 8, MFG-E8 whose expression has never been observed in cartilage [23].

Analytical, diagnostic and therapeutic context of MFGE8

• The BA46 antigen of the human milk fat globule (HMFG) membrane is expressed in human breast carcinomas and has been used successfully as a target for experimental breast cancer radioimmunotherapy [24].
• HMFG were present in stools of breast-fed neonates as shown by indirect immunofluorescence staining with a monoclonal antibody directed against carbohydrate residues present on HMFGM [9].
• For that purpose, we studied 54 commonly epithelial malignancies using immunohistochemistry (IHC) with a panel of seven frequently used MAb recognizing a gamut of membrane and cytoplasmic antigens (AE-1, CAM 5.2, B72.3, MC10, anti-carcinoembryonic antigen (anti-CEA), epithelial membrane antigen (EMA), and human milk fat globule (HMFG)) [25].
• Milk fat globule membrane (MFGM) enclosing fat droplets in human milk was found to contain a high molecular weight glycoprotein which did not migrate in 10% acrylamide gel on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) [20].
• The mucin antigen recognised by MAB G3F1 was detected by selectively extracting high molecular weight glycoprotein antigen from HMFG membrane using lectin affinity chromatography and gel filtration chromatography [26].

References