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Milk fat globule epidermal growth factor 8(MFGE8) is a multifunctional secreted glycoprotein encoded by MFGE8 gene, which is widely expressed in mammary epithelial cells, macrophages, astrocytes and tumor-associated fibroblasts, and can be released into extracellular matrix and body fluid microenvironment as a soluble bridging ligand. Compared with common integrin-binding cytokines, MFGE8 has a unique EGF repetitive sequence and a C-terminal coagulation factor-like domain, which can recognize phosphatidylserine (PS) on the surface of apoptotic cells and αvβ3/αvβ5 integrins on the surface of phagocytes at the same time, thus realizing bidirectional specific binding. In the process of physiological tissue renewal, the basal secretion of MFGE8 can efficiently mediate cell burial, accurately remove apoptotic cell debris, avoid the release of pro-inflammatory injury signals, maintain tissue immune homeostasis, and ensure wound repair and tissue remodeling in an orderly manner. However, in the tumor hypoxia microenvironment, tumor interstitial cells secrete a lot of MFGE8, and the extracellular accumulated MFGE8 can cross-link the integrin on the surface of tumor cells and endothelial cells, continuously activate PI3K/ERK signaling cascade, induce epithelial-mesenchymal transition of tumor cells, and promote pathological angiogenesis and distant metastasis of tumor. Other extracellular matrix bridging proteins can't compensate the unique PS- integrin two-way bridging function of MFGE8. The loss of MFGE8 will lead to the continuous accumulation of apoptotic fragments and induce the prolongation of chronic inflammation, while targeted neutralization of MFGE8 can significantly inhibit the progress of triple-negative breast cancer, ovarian cancer and other malignant tumors, which is the core irreplaceable target for the study of the mechanism of burial and the screening of tumor interstitial targeted drugs.
MFGE8 exists in interstitial fluid of tissues in the form of soluble ligands, and plays a bridging role by virtue of dual independent structural modules, specifically recognizing the phosphatidylserine residue of apoptotic cells and the integrin complex on the surface of phagocytes, respectively, and building a molecular bridge between cell recognition and signal transduction. Its unique bifunctional domain arrangement pattern forms a significant functional differentiation with the conventional extracellular matrix factors mediated by single domain, and constructs an exclusive regulatory pathway between apoptosis debris clearance and phagocytic immune response. Cell burial mediated by MFGE8 can link the apoptosis signal of tissue cells with the anti-inflammatory polarization state of macrophages, and dynamically balance the process of physiological tissue remodeling and the progress of pathological tumor invasion according to the oxygen supply level of microenvironment. This molecule is widely involved in physiological and pathological processes such as tissue regeneration after injury, removal of myelin fragments in central nervous system and metastasis of epithelial tumors. The loss of MFGE8 function will cause persistent local inflammatory lesions and weaken the body's inherent anti-tumor immune monitoring ability. To sum up, MFGE8 is the key target for the mechanism research of secretory bridging glycoprotein and the research and development of tumor interstitial targeted therapy.
Fig. 1 MFGE8 signaling via integrin αvβ5 in cellular signal transduction. MFGE8 (lactadherin) binds to αvβ5 integrin and modulates downstream signaling cascades, highlighting the receptor-mediated molecular basis of MFGE8 function in integrating extracellular cues to intracellular responses.1
The biological functions of bifunctional secreted MFGE8 lactadherin are fully focused on apoptotic PS capture and integrin-mediated tumor signal amplification:
Creative Biolabs offers high-quality MFGE8 proteins through optimized mammalian secretion systems, including full-length lactadherin and isolated EGF/coagulation domain variants. These products retain native PS-integrin dual binding activity, suitable for efferocytosis and anti-metastasis compound screening assays. All MFGE8 proteins undergo strict quality control to ensure consistent performance and reliable application across diverse immunology and oncology research platforms.
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Creative Biolabs provides custom-engineered MFGE8 stable cell lines, including tumor stromal overexpression and blank empty vector control models. These cell lines are optimized for secreted bridging glycoprotein profiling and metastatic signal functional analysis. Each cell line undergoes stringent validation to ensure stable expression profiles during long-term hypoxic cell culture, and can be widely deployed for large-scale anti-tumor stromal compound screening experiments.
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High-specificity recombinant antibodies targeting MFGE8 are developed via advanced antibody engineering technologies. These antibodies are validated for stromal cell secretion detection and breast/ovarian tumor tissue expression profiling, and can be combined with αvβ3 integrin detection reagents to analyze complete MFGE8 bridging complexes in tumor microenvironment cell models.
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Beyond catalog products, Creative Biolabs offers specialized custom services for MFGE8 research:
MFGE8 (lactadherin) acts as a bridging protein linking apoptotic PS and αv integrins to mediate silent efferocytosis and drive tumor invasion.
Tumor-secreted MFGE8 is a critical stromal factor promoting metastasis, a promising target for anti-stromal cancer therapy.
No, all MFGE8 products and services are strictly for research use only, not intended for clinical diagnosis or human therapeutic trials.
Offerings include full-length secreted MFGE8 glycoproteins, isoform-specific detection antibodies and custom stable cell lines for efferocytosis research.
MFGE8 proteins are validated via phosphatidylserine and integrin dual co-binding functional testing.