ESM1 regulates endothelial cell behavior and tumor microenvironments through multiple pathways:
Colorectal Cancer: Anti-ESM1 antibodies combined with bevacizumab reduced tumor growth by 58% in resistant models, downregulating DLL4 and MMP9 .
Prostate Cancer: ESM1 knockdown increased cell proliferation (cyclin D1↑, p21↓) and metastasis (MMP-9↑, TIMP-1↓) in PC3 and DU145 cells .
Endometrial Cancer (EC): High ESM1 expression correlated with advanced TNM stage, lymph node metastasis, and poor prognosis (P < 0.05) :
Clinicopathological Feature | High ESM1 (n=32) | Low ESM1 (n=32) | P-value |
---|---|---|---|
Histology Grade III | 14 | 7 | 0.025 |
Lymph Node Metastasis | 19 | 10 | 0.024 |
TNM Stage III–IV | 24 | 12 | 0.003 |
Viability: ESM1 silencing reduced endometrial cancer cell (AN3CA, RL95-2) viability by 40–60% at 72 hours .
Tumorigenicity: PC3 cells with ESM1 knockdown formed tumors 2.5× larger than controls in nude mice .
Therapeutic Development: Anti-ESM1 monoclonal antibodies are being explored to overcome bevacizumab resistance .
Biomarker Studies: Elevated serum ESM1 levels correlate with endothelial dysfunction in sepsis and cancer .
Mechanistic Studies: Used to dissect SPI1/ESM1 transcriptional regulation in endometrial cancer .
Endothelial cell-specific molecule 1 (ESM1), primarily found in the lung and kidney tissues, is a proteoglycan secreted by endothelial cells. Its mRNA expression is modulated by inflammatory cytokines. ESM1 plays a crucial role in the interactions between lung endothelial cells and leukocytes. Furthermore, ESM1 expression is observed in various epithelia and adipocytes. This molecule contributes to angiogenesis, particularly by promoting angiogenic sprouting. Its expression is upregulated by TNF alpha, IL1 beta, and lipopolysaccharide, while downregulated by IFN gamma. Notably, cells genetically engineered to overexpress ESM1 exhibit increased tumor formation, suggesting ESM1's potential involvement in tumor growth.
Recombinant human ESM1, produced in HEK293 cells, is a single, glycosylated polypeptide chain encompassing amino acids 20-184 (including a 10 amino acid C-terminal His tag). With a total of 175 amino acids, it has a calculated molecular mass of 19.5 kDa.
ESM1 is subjected to filtration (0.4 µm) and lyophilization from a 0.5mg/ml solution in phosphate buffered saline.
To prepare a working stock solution, add deionized water to the lyophilized pellet, aiming for a concentration of approximately 0.5mg/ml, and ensure complete dissolution. Prior to cell culture use, filter the reconstituted ESM1 solution through a sterile filter as it is not sterile.
Purity exceeding 95.0% as determined by SDS-PAGE analysis.
Endothelial cell-specific molecule 1, ESM-1, ESM1, endocan.
HEK293 cells.
WSNNYAVDCP QHCDSSECKS SPRCKRTVLD DCGCCRVCAA GRGETCYRTV SGMDGMKCGP GLRCQPSNGE DPFGEEFGIC KDCPYGTFGM DCRETCNCQS GICDRGTGKC LKFPFFQYSV TKSSNRFVSL TEHDMASGDG NIVREEVVKE NAAGSPVMRK WLNPR HHHHH HHHHH.
ESM1 is a glycosylated polypeptide chain consisting of 175 amino acids, including a 10 amino acid C-terminal His tag . The molecular mass of ESM1 is approximately 19.5 kDa . It is produced in HEK293 cells, a type of human embryonic kidney cell line, which allows for proper glycosylation and folding of the protein .
The expression of ESM1 is regulated by inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and lipopolysaccharide (LPS), while it is downregulated by interferon-gamma (IFN-γ) . This regulation suggests that ESM1 is involved in the body’s response to inflammation.
ESM1 has several important biological functions:
Due to its involvement in angiogenesis and inflammation, ESM1 has been identified as a potential biomarker for various diseases, including cancer . Its expression in endothelial cells and its regulation by inflammatory cytokines make it a significant target for therapeutic interventions aimed at modulating angiogenesis and inflammatory responses.
The recombinant form of ESM1 is produced in HEK293 cells, which ensures that the protein is properly glycosylated and folded . The recombinant protein is available as a lyophilized powder and can be reconstituted in phosphate-buffered saline for laboratory research use . It is important to note that the recombinant ESM1 is not sterile and should be filtered before use in cell culture .