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MFGE8

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

Background

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 Schematic diagram illustrating MFGE8 binding to αvβ5 integrin and downstream signaling involving PTP1B, insulin receptor, IRS-1 and GLUT-4. (OA Literature)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

MFGE8 Protein Function: Core Roles in Efferocytic Bridging and Tumor Invasion Tuning

The biological functions of bifunctional secreted MFGE8 lactadherin are fully focused on apoptotic PS capture and integrin-mediated tumor signal amplification:

  • Bridging function of apoptotic phosphatidylserine: it can specifically bind phosphatidylserine (PS) of apoptotic cells everted to the outside of cell membrane, accurately identify aging and damaged dead cells, and provide molecular recognition basis for subsequent burial clearance effect, which is the key precondition for initiating programmed cell clearance.
  • Integrin co-crosslinking regulation: It can simultaneously cross-link αvβ3 and αvβ5 integrin receptors on the surface of macrophages and tumor cells, build specific signal connection between cells, and couple extracellular matrix recognition and intracellular signal transduction to realize two-way cell function regulation.
  • Regulation of anti-inflammatory burial: Mediating the process of clearing the debris of silent apoptotic cells, avoiding the release of pro-inflammatory signals and the activation of inflammatory waterfalls while effectively clearing the dead cells of tissues, effectively inhibiting the inflammatory damage of tissues and maintaining the immune homeostasis of local tissues.
  • Regulation of tumor metastasis process: by activating PI3K/ERK signaling pathway, it can effectively promote tumor cell migration and invasion, induce tumor epithelial-mesenchymal transition, and at the same time drive pathological angiogenesis, and continuously promote malignant proliferation and distant metastasis of solid tumors.
  • Pathological characteristics of the disease: Abnormal high expression of MFGE8 in tumor stroma is highly correlated with the malignant metastasis phenotype of triple negative solid tumor, which can be used as an important molecular marker to indicate tumor progress, metastasis risk and poor prognosis.

MFGE8 Protein Product

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.

MFGE8 Protein Product

Not finding the membrane protein product you need? Contact us to start your one-stop custom service!

MFGE8 Stable Cell Line Product

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.

MFGE8 Stable Cell Line Product

Not finding the stable cell line product you need? Contact us to start your one-stop custom service!

MFGE8 Recombinant Antibody Product

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.

MFGE8 Recombinant Antibody Product

Not finding the recombinant antibody product you need? Contact us to start your one-stop custom service!

Product Features

  • Native Dual PS-Integrin Binding Activity: Preserves intact efferocytic bridging capacity for stromal tumor research.
  • MFGE8 Isoform Specificity: Eliminates non-specific cross-recognition of unrelated ECM glycoproteins.
  • Immuno-Oncology Compatibility: Optimized reagent series for efferocytosis and metastatic tumor screening workflows.
  • Comprehensive Customization Support: Facilitates end-to-end development of customized proteins, antibodies and stable cell lines to address bridging ligand research demands.

Custom MFGE8 Research Services

Beyond catalog products, Creative Biolabs offers specialized custom services for MFGE8 research:

  • Custom MFGE8 Protein Production: Tailored mutant and fluorescent-tagged MFGE8 constructs for PS-integrin binding analysis.
  • Custom Antibody Development: Generation of highly specific MFGE8 antibodies for tumor stromal tissue immunostaining.
  • Stable Cell Line Engineering: Construction of customized MFGE8-overexpressing fibroblast tumor in vitro models.
  • Functional Assay Development: Custom design of efferocytosis and tumor migratory quantitative detection workflows.

Frequently Asked Questions (FAQ)

  1. What is the primary function of MFGE8?

    MFGE8 (lactadherin) acts as a bridging protein linking apoptotic PS and αv integrins to mediate silent efferocytosis and drive tumor invasion.

  2. Why is MFGE8 a significant research target?

    Tumor-secreted MFGE8 is a critical stromal factor promoting metastasis, a promising target for anti-stromal cancer therapy.

  3. Are Creative Biolabs' MFGE8 products suitable for clinical use?

    No, all MFGE8 products and services are strictly for research use only, not intended for clinical diagnosis or human therapeutic trials.

  4. What types of MFGE8 products does Creative Biolabs offer?

    Offerings include full-length secreted MFGE8 glycoproteins, isoform-specific detection antibodies and custom stable cell lines for efferocytosis research.

  5. How are MFGE8 proteins validated for activity?

    MFGE8 proteins are validated via phosphatidylserine and integrin dual co-binding functional testing.

Reference
  1. Datta, Ritwik, et al. "PTP1B mediates the inhibitory effect of MFGE8 on insulin signaling through the β5 integrin." Journal of Biological Chemistry 300.2 (2024). Under Open Access license CC BY 4.0, without modification. https://doi.org/10.1016/j.jbc.2024.105631
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