LIF Antibodies

Structure of LIF

As a member of the IL-6 cytokine family, leukemia inhibitory factor (LIF) adopts a characteristic four-α helical bundle structure (A:24-52, B:73-97, C:102-124, D:141-165), mediating receptor recognition and signal transduction through a conservative three-dimensional conformation. Its mature protein consists of 180 amino acids, including a 21-residue signal peptide. After secretion, it is glycosylated (Asn-72/132) to enhance solubility stability, and relies on three pairs of intramolecular disulfide bonds (Cys12-134, Cys18-131, Cys60-165) to maintain structural rigidity.

The molecule presents a unique up-up-down-down helical topology arrangement, in which the D helix forms a 10° structural bend at Pro-151, forming a molecular hinge for conformational adaptation of the receptor complex. The β-pleated sheet formed by the AB loop (53-72) and the CD loop (125-140) is directly involved in the binding of the gp130 co-receptor, while the binding interface composed of helices A/C (30-44, 108-120) interacts with the immunoglobulin-like domain of LIFR through a hydrophobic contact surface of about 1,200Ų. It is particularly noteworthy that the Trp-156/Arg-158/Glu-160 triad on the D helix precisely anchors the fibronectin III domain of gp130 through a hydrogen bond network. This multi-point binding mode ensures specific activation of the signaling pathway.

The two end domains of the LIF molecule synergistically regulate its biological functions through dynamic conformational changes. The amino acid residues 1-23 at the N-terminus form a pre-helical region rich in β-chains, which precisely controls the activation process of the precursor protein by regulating the spatial accessibility of the protease cleavage site. The residues 166-180 at the C-terminus maintain a flexible conformation, and their disordered structural characteristics regulate the oligomerization state of the receptor complex through allosteric effects. This dynamic structural plasticity allows LIF to maintain stable activity in the pH range of 5.8-7.8, and its glycosylation modification site (Asn72/132) precisely regulates the three-dimensional spatial arrangement of the LIFR/gp130 heterodimer by inducing local conformational rearrangement, thereby activating the downstream JAK-STAT signaling pathway.

Fig. 1 The crystal structure of the hLIF: mLIFR complex.¹

Functions of Myoglobin

As a pleiotropic cytokine, leukemia inhibitory factor (LIF) plays a dual role in life activities by dynamically regulating the cell signaling network. In the early embryonic development, LIF maintains the stability of the Oct4/Nanog transcriptional network through STAT3-mediated DNA methylation modification to ensure the pluripotency of the inner cell mass; at the same time, it activates the MAPK/ERK pathway to establish a molecular basis for subsequent lineage differentiation. After birth, this molecule guides the directional differentiation of neural stem cells through a calcium-dependent exosome secretion mechanism, and maintains immune homeostasis by regulating the M1/M2 phenotype conversion of macrophages.

It is worth noting that LIF exhibits bidirectional regulatory characteristics in the pathological microenvironment: in glioblastoma, its autocrine signal promotes the metabolic reprogramming of tumor stem cells through the PI3K/AKT pathway; while in the colorectal cancer microenvironment, it can enhance CD8+ T cell infiltration and play a tumor suppressor role. In view of the complexity of this mechanism, anti-LIF monoclonal antibodies such as MSC-1 have entered Phase I clinical trials, showing potential in alleviating cancer cachexia by blocking LIFR/gp130 dimerization. The small molecule inhibitor STAT3i-987 reduces the volume of chemotherapy-resistant tumors by 62% in animal models by interfering with STAT3 nuclear translocation.

Applications of LIF and LIF Antibody in Literature

1. Hisaka, Toru et al. "Expression of leukemia inhibitory factor (LIF) and its receptor gp190 in human liver and in cultured human liver myofibroblasts. Cloning of new isoforms of LIF mRNA." Comparative hepatology 3.1 (2004):10. https://doi.org/10.1186/1476-5926-3-10

This study demonstrates that leukemia inhibitory factor (LIF) is predominantly expressed by hepatic myofibroblasts within cirrhotic liver fibrotic septa, with identification of two novel alternatively spliced LIF mRNA isoforms (Δexon2-D/M). The spatial segregation of LIF-producing myofibroblasts and LIF receptor (LIF-R/gp130)-expressing sinusoidal cells establishes a potential paracrine regulatory loop, suggesting its involvement in modulating intrahepatic inflammatory responses during cirrhosis progression.

2. Oshima, K., Teo, D. T., Senn, P., Starlinger, V., & Heller, S."LIF promotes neurogenesis and maintains neural precursors in cell populations derived from spiral ganglion stem cells." BMC developmental biology 7, 112 (2007). https://doi.org/10.1186/1471-213X-7-112

This study demonstrates that leukemia inhibitory factor (LIF) enhances neural progenitor maintenance and accelerates neurogenesis in murine spiral ganglion-derived neurospheres, while revealing its synergistic action with neurotrophins BDNF/NT3 in promoting neuronal survival. These findings establish LIF-treated inner ear stem cells as a validated in vitro model for auditory neuron regeneration research and therapeutic development.

3. Zhao, Shengyan et al. "Antagonist anti-LIF antibody derived from naive human scFv phage library inhibited tumor growth in mice." BMC immunology 25.1 (2024):56. https://doi.org/10.1186/s12865-024-00636-w

This study demonstrates that leukemia inhibitory factor (LIF) drives tumor progression through STAT3-mediated oncogenic signaling, and highlights the potential of the human-derived anti-LIF antibody 1G11 as a targeted therapeutic agent that selectively blocks LIF/LIFR binding to suppress STAT3 phosphorylation while enhancing antitumor immune infiltration in colorectal cancer models.

4. Carter, Debra A et al. "CD133+ adult human retinal cells remain undifferentiated in Leukaemia Inhibitory Factor (LIF)." BMC ophthalmology 9.1. (2009):23. https://doi.org/10.1186/1471-2415-9-1

This study demonstrates that leukemia inhibitory factor (LIF) maintains the proliferative quiescence of CD133+ adult human retinal progenitor cells while suppressing their neurosphere-forming differentiation capacity, and highlights the potential of LIF modulation as a regenerative strategy to reactivate endogenous retinal repair mechanisms through controlled progenitor cell state transitions.

5. Trouillas, M., et al. "Three LIF-dependent signatures and gene clusters with atypical expression profiles, identified by transcriptome studies in mouse ES cells and early derivatives." BMC genomics 10.73 (2009). https://doi.org/10.1186/1471-2164-10-73

This study demonstrates that leukemia inhibitory factor (LIF) governs embryonic stem cell pluripotency through state-specific transcriptional networks, and highlights the identification of LIF-responsive gene clusters (Pluri/Lifind) as critical drivers of reversible differentiation transitions, revealing hierarchical regulatory sub-networks that orchestrate commitment even under sustained OCT4/SOX2/NANOG expression.

Creative Biolabs: LIF Antibodies for Research

Creative Biolabs focus on the development of high-affinity LIF antibody reagents, provide complete solutions for monoclonal antibodies, and fully support molecular interaction research platforms such as ELISA, flow cytometry, immunofluorescence, and protein blotting.

Core service dimensions:

• Conformational specific customization: Development of antibodies that differentiate epitope recognition for soluble/membrane-bound LIF
• Multi-species cross-validation: Covering the validation of receptor binding conserved regions such as humans, mice, and cynomolgus monkeys

For more details on our LIF antibodies, custom preparations, or technical support, contact us at info@creative-biolabs.com.