PRT-01 / Prothelia, University of Nevada, AstraZeneca - LARVOL DELTA

Spatial-proteomics reveals recombinant human laminin-111 restores adhesion-signaling to laminin-α2 deficient muscle. (PubMed, JCI Insight) - "Treatment with recombinant human laminin-111 (rhLAM-111) restored protein localization, reduced ROS, and promoted glycolytic, pro-survival signaling. These findings highlight laminin's role in maintaining muscle homeostasis and metabolism and support the therapeutic potential of rhLAM-111 for treating LAMA2-CMD by restoring adhesion and intracellular signaling in dystrophic muscle."

Journal • CNS Disorders • Genetic Disorders • Muscular Dystrophy • LAMA2 • MAPK8

Technetium-99m radiolabeling of HYIGSR peptide for in vivo and ex vivo assessment as a biomarker in breast cancer (EANM 2025) - "Recent studies have drawn attention to bioactive peptides derived from laminin-111, an extracellular matrix protein implicated in tumor progression...Despite its favorable physicochemical properties, ex vivo biodistribution studies and scintigraphic images revealed limited tumor uptake, probably due to low in vivo stability of the radiolabeled compound, indicating that further structural modifications may be required to improve its tumor-targeting efficiency. This work was supported by FAPESP: Grant #2021/10265-8, CancerThera/CEPID."

Preclinical • Breast Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma

MSC1 Cells Suppress Colorectal Cancer Cell Growth via Metabolic Reprogramming, Laminin-Integrin Adhesion Signaling, Oxidative Stress Resistance, and a Tumor-Suppressive Secretome. (PubMed, Biomedicines) - " Network analysis revealed six tumor-suppressive mechanisms of MSC1 cells: (i) Metabolic reprogramming via enhanced glucose and lipid uptake, phosphoinositide signaling, and membrane/protein recycling, (ii) Robust antioxidant defenses, including SOS signaling and system xc⁻, (iii) Extracellular matrix stabilization and laminin-111-integrin-mediated adhesion, (iv) Secretome with direct anti-cancer effects, (v) Regulation of survival and cancer-associated fibroblasts (CAFs) formation inhibition through balanced proliferation, apoptosis, and epigenetic signals, (vi) Controlled pro-inflammatory signaling with anti-inflammatory feedback... This study provides the first mechanistic map of MSC1's tumor-suppressive functions in CRC, extending beyond immunomodulation to include metabolic competition, ECM stabilization, and anti-cancer secretome activity. These findings establish MSC1 cells as a novel therapeutic strategy for CRC in cell-based cancer therapies."

Journal • Colorectal Cancer • Immunology • Oncology • Solid Tumor • CAFs • TLR4

Lack of biochemical signalling in GelMA leads to polarity reversion in intestinal organoids independent from mechanoreciprocity. (PubMed, J Tissue Eng) - "Here, we studied effects of mechanical properties of GelMA and addition of laminin-111 on encapsulation and growth of small intestinal organoids...Collectively, our study confirms that tuning of GelMA mechanical properties alone cannot recapitulate the basal membrane matrix. However, controlled polarity reversion offers a tool for engineering organoids and enabling apical membrane access."

Journal • Oncology • Sarcoma • Solid Tumor

Enhancing human pluripotent stem cell differentiation to cardiomyocytes through cardiac progenitor reseeding and cryopreservation. (PubMed, iScience) - "Reseeding during differentiation also enables transition to defined extracellular matrices, including fibronectin, vitronectin, and laminin-111, which all supported hPSC-derived EOMES+ mesoderm and ISL1+/NKX2-5+ cardiac progenitor differentiation to CMs. In summary, we present a method to increase hPSC-CM differentiation purity and demonstrate that specific CM progenitors are amenable to cryopreservation."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • VTN

Localizations of Laminin Chains Suggest Their Multifaceted Functions in Mouse Tooth Development. (PubMed, Int J Mol Sci) - "Laminin 111 was localized in the extracellular matrix of the apical dental papilla without forming a visible basement membrane. These findings suggest the multifaceted functions of laminins in tooth development and set the foundation for functional investigations."

Journal • Preclinical

NaBC1 Boron Transporter Enables Myoblast Response to Substrate Rigidity via Fibronectin-Binding Integrins. (PubMed, Adv Sci (Weinh)) - "These effects are fibronectin and NaBC1-mediated as they are abrogated in hydrogels coated with laminin-111 in place of fibronectin and in esiRNA NaBC1-silenced cells. These findings thus demonstrate that NaBC1 controls boron homeostasis and also functions as a mechanosensor."

Journal

Comparison of equine-induced pluripotent stem cell characteristics induced on different cell adhesion substrates. (PubMed, Vet J) - "The reprogramming efficiency of cells induced on the E8 fragment of laminin-511 (eiPSC-511) was higher than that on Geltrex containing laminin-111 as a major laminin (eiPSC-111), and supplementation with a cocktail of small molecular compounds increased the number of iPSC colonies on both substrates...On the contrary, although no significant differences were observed in the histology of teratomas, increased in vitro differentiation into three germ layers in eiPSC-111 was shown compared to those in eiPSC-511. Thus, these results contributed to the improved generation of iPSC in horses."

Journal • Oncology • ITGA3 • ITGA6 • ITGA7

Interactions between ADGRF1 (GPR110) and extracellular matrix proteins govern its effects on tumorigenesis in HER2-positive breast cancer. (PubMed, Br J Pharmacol) - "ADGRF1 switches from a tumour-promoting to tumour-suppressive function upon interaction with laminin-111, leading to improvements in sensitivity to anti-HER2 drugs. Leveraging ADGRF1 interactions with laminin-111 may allow the design of novel therapies against ADGRF1 in HER2+ BC."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Scientific and Technological Prospecting on Polymeric Particles Containing Extracellular Matrix Peptides for the Treatment of Duchenne Muscular Dystrophy. (PubMed, Recent Adv Drug Deliv Formul) - "Extracellular matrix-derived peptides (eg laminin-111 derivatives) and the use of essential oils with antiinflammatory activity in polymeric particles for application in the treatment of Duchenne muscular dystrophy are discussed...Many patents focus on palliative technologies that seek to prolong the progressive effects of the disease, considering the control of the inflammatory process. The technological and scientific prospecting suggests the need for continuous research on systems that can serve as a treatment for Dystrophy."

Journal • CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Respiratory Diseases

Integrin-activating Yersinia protein Invasin sustains long-term expansion of primary epithelial cells as 2D organoid sheets. (PubMed, Proc Natl Acad Sci U S A) - "Here, we show that interaction between Matrigel's major component laminin-111 with epithelial α6β1-integrin is crucial for this process...The 2D "organoid sheet" format holds advantages over the 3D "in gel" format in terms of imaging, accessibility of basal and apical domains, and automation for high-throughput screening. Invasin represents a fully defined, affordable, versatile, and animal-free complement to Matrigel®/BME®."

Journal • Gastroenterology

Integrin a3b1 Regulates Alveolar Basement Membrane Formation during Distal Lung Development through Epithelial Differentiation (AAP-NCE 2024) - "AECs deficient in a3b1 produced abnormal laminin isoforms, with persistence of embryonic laminin-111 and failure to produce AT1-derived mature laminin-332 isoforms at P28, indicating failed developmental programming of laminin isoform switching due to loss of AT1... Epithelial a3b1 is required for distal lung development through regulation of AEC differentiation, which directs proper laminin isoforms switching essential for alveolar BM formation."

Developmental Disorders • Musculoskeletal Diseases • Orthopedics

Spatial-omics protein analysis of LAMA2-related muscular dystrophy patients and mouse model: Exploring the therapeutic potential of recombinant human laminin-111 (New Directions 2024) - No abstract available

Preclinical • Muscular Dystrophy • LAMA2

Continuous protein-density gradients: A new approach to correlate physical cues with cell response. (PubMed, PNAS Nexus) - "In this study, we introduce a strategy for depositing ultrathin films comprised of laminin-111 with precisely controlled biophysical gradients onto planar substrates using the Langmuir-Blodgett (LB) technique...Furthermore, human adipose-derived stem cells were seeded onto the gradient films to investigate the influence of protein density on cell attachment, showing that the distribution of the cells can be modulated by the arrangement of the laminin at the air-water interface. The presented approach not only allowed us to gain insights into the intricate interplay between biophysical cues and cell behavior within complex tissue environments, but it is also suited as a screening approach to determine optimal protein concentrations to achieve a target cellular output."

Journal

Netrin-1 As A Neural Guidance Protein In Development And Reinnervation Of The Larynx. (PubMed, Ann Anat) - "This paper reviews the known functions of Netrin-1 during the formation of the central nervous system and during cranial nerve primary innervation. It also describes the role of Netrin-1 in the formation of the larynx and during recurrent laryngeal reinnervation following nerve injury in the adult."

Journal • NTN1

Observing Dynamic Conformational Changes within the Coiled-Coil Domain of Different Laminin Isoforms Using High-Speed Atomic Force Microscopy. (PubMed, Int J Mol Sci) - "Finally, we observed the dynamic rearrangement of the C-terminal LG domains of laminin-111 and laminin-332, switching them between compact and open conformations. Thus, HS-AFM can directly visualize molecular rearrangement processes within different laminin isoforms and provide dynamic structural insight not available from other microscopy techniques."

Journal

Analysis of SIKVAV's receptor affinity, pharmacokinetics, and pharmacological characteristics: a matrikine with potent biological function. (PubMed, J Biomol Struct Dyn) - "Laminin α1-derived peptide (SIKVAV) is a bioactive peptide derived from laminin-111 that participates in tumor development, cell proliferation, angiogenesis in various cell types...Our analysis suggests that SIKVAV has a high probability of interacting with peroxisome proliferator-activated receptor-gamma (NR-PPAR-γ), which has anti-inflammatory activity. The results of bioinformatics can help understand the participation of SIKVAV in homeostasis and influence the understanding of how this peptide can act as a biological asset in the control of dystrophies, neurodegenerative diseases, and tissue engineering.Communicated by Ramaswamy H. Sarma."

Journal • PK/PD data • Alzheimer's Disease • CNS Disorders • Muscular Dystrophy • Oncology • PPARG

Assessment of bioactive peptides derived from laminin-111 as prospective breast cancer-targeting agents. (PubMed, Amino Acids) - "These results signify the effective penetration of YIKVAV and YIGSR into tumor tissue. Therefore, the synthesized α1 and β1 peptide fragments exhibit favorable characteristics as potential breast cancer-targeting agents, promising future exploration as radiopharmaceuticals for breast cancer."

Journal • Breast Cancer • Oncology • Solid Tumor

Laminin-Augmented Decellularized Extracellular Matrix Ameliorating Neural Differentiation and Neuroinflammation in Human Mini-Brains. (PubMed, Small) - "As augmenting strategy, laminin 111 supplement promotes neural function by synergic effect with laminin 521 in P-BdECM...Further, supplementation of the brain-specific molecule to non-neural matrix also ameliorated glial cell inflammation as in P-BdECM. In conclusion, P-BdECM-augmentation strategy can be used to recapitulate humanized pathophysiological cerebral environments for neurological study."

Journal • Inflammation • ANXA1

Macrophage migration is differentially regulated by fibronectin and laminin through altered adhesion and myosin II localization. (PubMed, Mol Biol Cell) - "Laminin 111 inhibits macrophage cell spreading, but drives them to migrate rapidly and less persistently compared to cells on fibronectin...The role of ECM composition in dictating motile and inflammatory responses in 3D and in vivo contexts warrants further study. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text]."

Journal • Inflammation

The laminin-keratin link shields the nucleus from mechanical deformation and signalling. (PubMed, Nat Mater) - "Coating substrates with laminin-111-unlike fibronectin or collagen I-impairs cell response to substrate rigidity and YAP nuclear localization...In turn, this affects the nuclear YAP mechanoresponses, chromatin methylation and cell invasion in three dimensions. Our results demonstrate a mechanism by which tissues can regulate their sensitivity to mechanical signals."

Journal

Mechanobiology: Border crosstalk protects the nucleus from stress. (PubMed, Curr Biol) - "A new study reports that the extracellular matrix component laminin-111 shields the nucleus from actin-mediated forces by engaging the keratin cytoskeleton. Thus, matrix composition represents a means by which tissues can protect cell nuclei from mechanical damage."

Journal

Fabrication of oxygen-carrying microparticles functionalized with liver ECM-proteins to improve phenotypic three-dimensional in vitro liver assembly, function, and responses. (PubMed, Biotechnol Bioeng) - "Next, to allow for integrin engagements the surfaces of these MPs were functionalized using liver ECM proteins including fibronectin, laminin-111, laminin-511, and laminin-521, then they were used to assemble composite spheriods along with HepG2 cells and HSCs...Furthermore, hepatocytes and HSCs exhibited more pronounced phenotypic arrangements when cocultured with laminin-511 and 521 modified MPs providing clear evidence that specific ECM proteins have distinctive roles in the phenotypic regulation of liver cells in engineering 3D spheroids. This study advances efforts to create more physiologically relevant organ models allowing for well-defined conditions and phenotypic cell signaling which together improve the relevance of 3D spheroid and organoid models."

Journal • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • CDH1 • VCL

Laminin switches terminal differentiation fate of human trophoblast stem cells under chemically defined culture conditions. (PubMed, J Biol Chem) - "Strikingly, presence of a single additional extracellular cue - laminin-111 - switched the terminal differentiation of hTSCs from STB to the EVT lineage under these conditions...On the other hand, TGFβ inhibition prevented STB formation of hTSCs. The chemically defined culture system for hTSC differentiation established herein facilitates quantitative analysis of heterogeneity that arises during hTSC differentiation and will enable mechanistic studies in vitro."

Journal • EPAS1 • HIF1A • NOTCH1

Design and Development of Extracellular Matrix Protein-based Microcapsules as Tools for Bacteria Investigation. (PubMed, Adv Healthc Mater) - "We generated hollow ECM-based microcapsules from laminin-111 or laminin-111/collagen IV to investigate the behavior of organisms within confined 3D extracellular matrices...The release of E. coli-laden ECM-based protein microcapsules into a physiological environment revealed differences in the dynamic behavior of E. coli depending on the constitution of the surrounding ECM protein matrix. The developed ECM-based protein microcapsules have the potential to be implemented in several biomedical applications, including the design of in vitro infection models."

Journal • Infectious Disease