CLDN7 (Ab-210) Antibody
Description
Antigen Specificity and Design
CLDN7 (Ab-210) antibody recognizes the phosphorylated tyrosine 210 site on human Claudin-7, a key post-translational modification linked to cellular signaling and disease mechanisms.
-
Immunogen: Synthetic phosphopeptide derived from the sequence around Tyr210 (S-K-E-Y(p)-V) .
-
Cross-Reactivity: Validated for human, mouse, and rat samples .
-
Target Function: Claudin-7 is a tight junction protein involved in cell polarity and barrier function. Dysregulation is associated with cancers, including colorectal and renal carcinomas .
Cancer Metastasis and EMT Studies
-
CLDN7 phosphorylation at Tyr210 is implicated in epithelial-mesenchymal transition (EMT), enhancing tumor cell motility and invasiveness. Knockdown of CLDN7 reduces metastasis in colorectal cancer models .
-
The antibody enables detection of phosphorylated CLDN7 in pathways involving TACE/presenilin2-mediated EpCAM cleavage, a driver of EMT .
Tight Junction Dynamics
-
CLDN7 forms complexes with EpCAM, which are critical for rapid tight junction (TJ) repair. Loss of CLDN7 disrupts TJ strand networks, increasing paracellular permeability .
-
The antibody aids in studying TJ remodeling during injury or carcinogenesis .
Validation Data
-
Western Blot: Detects a single band at ~22 kDa in human Caco-2 lysates, aligning with CLDN7’s molecular weight .
-
Immunohistochemistry (IHC): Strong staining in renal clear cell carcinoma, gallbladder adenocarcinoma, and rectal cancer tissues .
-
Specificity: No cross-reactivity with non-phosphorylated CLDN7 due to affinity purification against phosphopeptides .
Research Significance
CLDN7 (Ab-210) antibody is pivotal for:
Product Specs
Target Background
- This research demonstrates that TGF-beta1 alters esophageal epithelial barrier function by reducing claudin-7 expression in eosinophilic esophagitis. PMID: 28832026
- In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, requiring further investigation to understand their role in the pathogenesis of corneal astigmatism. (Meta-analysis) PMID: 29422769
- The current study revealed distinct expression patterns of claudin5, 7 and 8 in nonneoplastic mucosal tissues and gastric carcinoma tissues. Furthermore, the expression of these claudin proteins was strongly associated with metastatic progression and prognosis in patients with gastric carcinoma. PMID: 29901188
- DICFM approach may be applied as an appropriate method to quantify the immunohistochemical staining of claudin-7 on the cell membrane and claudin-7 may serve as a marker for identification of lung cancer. PMID: 29512497
- Cycling hypoxia could induce significant changes in CLDN1 and CLDN7 expression in nasopharyngeal cancer cells, indirectly regulating P18 expression and influencing cell invasion/proliferation. PMID: 28055967
- These findings identify EpCAM as a substrate of matriptase and link HAI-2, matriptase, EpCAM, and claudin-7 in a functionally important pathway that causes disease when it is dysregulated. PMID: 28094766
- 84/118, 64/118, 52/118 reaction with claudin-1, claudin-3 and claudin-4 in cancer and colon polyps exhibited a membrane localization, respectively. Mislocalization of claudin-3 to the nucleus in colon cancer and mislocalization of claudin-4 to the nucleus in adenomas of the colon were detected for the first time. PMID: 28295005
- This suggests that the reduction of CLDN5, 7, and 18 expression diminishes the suppressive ability of interaction between PDK1 and Akt, resulting in sustained phosphorylation of Akt, leading to disordered proliferation in lung squamous carcinoma cells. PMID: 27884700
- These results indicate that the dysregulated expression of these miRNAs, in conjunction with the high claudin 1 levels, could serve as a valuable biomarker that identifies a subset of tumors within the poorly characterized basal-like subtype of breast cancer. PMID: 26982264
- The expression of claudin-7 does not show any significant difference between cervical carcinoma tissues and adjacent non-neoplastic tissues. PMID: 26464708
- We identified hepatocyte nuclear factor 4alpha as a regulatory factor that bound endogenous CLDN7 promoter in differentiating intestinal epithelial cells and stimulated CLDN7 promoter activity. PMID: 26216285
- We identified a previously unrecognized function of claudin-7 in regulating cell proliferation and maintaining epithelial cell attachment through engaging integrin beta1. PMID: 26081244
- A variant, rs222857, in the CLDN7 locus, was predicted to increase adiponectin levels within intensive lifestyle intervention. PMID: 25759378
- CLDN-7 palmitoylation prevents tight junction integration and promotes glycolipid-enriched membrane domains recruitment. Through associated molecules, palmitoylated CLDN-7 supports motility and invasion. PMID: 26054340
- The increased claudin-1 expression was significantly associated with high pathologic grade, the presence of microscopic perineural invasion, vascular invasion, nodal metastasis, and advanced clinical stage of oral squamous cell carcinoma. PMID: 25078758
- Data indicate that claudin-7 knockdown cells display decreased anchorage-independent growth. PMID: 25514462
- Loss of claudin-7 enhances epithelial-to-mesenchymal transition to promote colon cancer, in a manner dependent on Rab25. PMID: 25500541
- Increased claudin 7 expression was related to decreased survival in nasopharyngeal carcinoma. PMID: 25778318
- Increased expression of claudin-7 is associated with liver cirrhosis and hepatocellular carcinoma. PMID: 24696415
- This study suggests the possibility that EpCAM, together with CD44v6 and claudin-7 as well as ALDH1, may be involved in the development of the aggressive phenotype of anaplastic thyroid carcinoma. PMID: 24727741
- These findings confirm the role of claudin-1 as a promoter of colon tumorigenesis and further identify the role of the dysregulated antigen-tumor interaction and inflammation in claudin-1-dependent upregulation of colon tumorigenesis. PMID: 24997475
- Evaluated expression of claudins in gastric cancer and determined their significance for patient outcome. Claudin-3 and claudin-7 were expressed in 25.4% and 29.9% of gastric cancer tissues; 51.5% of gastric cancer tissues had reduced claudin-18. PMID: 24333468
- These results suggest aberrant Claudin 7, alpha - and beta-catenin expression and/or localisation patterns may be putative markers for distinguishing localised prostate cancer from aggressive metastatic disease when used collectively. PMID: 24358122
- The CLDN7 rs4562 (c.590C>T) genotype had a higher risk of lymph node involvement and a lower degree of tumor differentiation. PMID: 24479816
- The lack of claudin-7 expression in the tumor center may be used to identify patients with an increased risk for regional recurrence. PMID: 23953778
- Claudin-7 was phosphorylated at serine 204 by protein kinase C. PMID: 23433123
- Survival analysis showed a trend toward a better prognosis among patients with overexpression of claudin-7 in hepatocellular carcinoma. PMID: 23146509
- Increased expression of claudin-1 contributes to an anti-apoptotic role in TNF-alpha-induced apoptosis. PMID: 22941467
- CD24+ (P=0.07) and claudin-7 positivity (P=0.05) were associated with reduced time of recurrence, suggesting a contribution of these markers to the aggressiveness of breast cancer. PMID: 21956537
- Claudin-7 and tricellulin were markedly reduced at all stages of tumor development. In situ hybridization analysis showed no correlation between HPV infection and altered expression of the tight junction proteins. PMID: 21480761
- Claudin-7 is significantly upregulated in epithelial ovarian cancer. PMID: 21789222
- Down-regulation of Claudin-7 and overexpression of Slug in lung squamous cell carcinoma and adenocarcinoma. PMID: 21645451
- The claudin-7 inhibits cell migration and invasion through the ERK/MAPK signaling pathway in response to growth factor stimulation in human lung cancer cells. PMID: 21641901
- Transcriptional activity of the claudin 7 gene is not a useful marker of laryngeal tumor. PMID: 21193919
- Claudin-7 mRNA level is decreased already as an early event in colorectal carcinogenesis, probably contributing to the compromised epithelial barrier in adenomas. PMID: 21310043
- Claudin-7 down-regulation is an important feature in oral squamous cell carcinoma. PMID: 21083599
- These data suggest that proteasomes regulate claudin-1 localization at the plasma membrane, which changes upon proteasomal inhibition to a Rab5a-mediated endosomal localization. PMID: 20926780
- Increased expression of claudin-6, claudin-7, or claudin-9 is sufficient to enhance tumorigenic properties of a gastric adenocarcinoma cell line. PMID: 20874001
- Claudins 6, 7, and 9 expressions are closely related to gastric carcinogenesis. PMID: 19960275
- Claudin-1 was expressed in all 18 cases of Epstein-Barr virus-associated nasopharyngeal carcinoma studied. PMID: 20204275
- Loss of claudin-7 correlates with histological grade in both ductal carcinoma in situ and invasive ductal carcinoma of the breast, providing insight into the potential role of CLDN-7 in the progression and ability of breast cancer cells to disseminate. PMID: 12673207
- Two forms of claudin-7, a full-length form with 211 AA residues and a C-terminal truncated form with 158 AA residues, are able to regulate the expression of a tissue-specific protein, prostate-specific antigen, in the LNCaP prostate cancer cell line. PMID: 14502431
- Loss of claudin-1 expression proved to be a strong predictor of disease recurrence and poor patient survival in stage II colon cancer. PMID: 15475928
- Claudin-1 and claudin-7 may play a significant role in tumor progression of cervical neoplasia and may represent useful markers for malignant transformation of cervical squamous cells. PMID: 15790437
- Overexpression of claudin-7 is associated with gastric tumorigenesis. PMID: 16049341
- Induction of claudin7 expression by ELF3 appears critical to the formation of the epithelial structures in biphasic synovial sarcoma. PMID: 17060315
- When compared, adenocarcinomas and squamous cell carcinomas revealed significant differences in CLDN7 expression. PMID: 17418912
- Claudin-7-associated EpCAM is recruited into (tetraspanin-enriched membrane microdomains) and forms a complex with CO-029 and CD44v6 that facilitates metastasis formation. PMID: 17579117
- Results show that claudin 7 expression changed with the gastric carcinogenic process and that this is implicated in cancer characteristics. PMID: 17611659
- Claudin-7 is a candidate expression marker for distinguishing chromophobe renal cell carcinoma from other renal tumor subtypes, including the morphologically similar oncocytoma. PMID: 17922590
Q&A
How can researchers validate the specificity of CLDN7 (Ab-210) antibody in detecting Tyr210 phosphorylation?
Methodological Answer:
To validate specificity, combine knockdown experiments (siRNA/shRNA targeting CLDN7) with peptide blocking assays using the immunogen sequence (S-K-E-Y(p)-V) . Parallel Western blotting with lysates from phosphorylated (e.g., cisplatin-treated lung cancer cells) vs. non-phosphorylated samples (phosphatase-treated) can confirm target recognition. Include isotype-matched IgG controls in immunohistochemistry (IHC) to rule out non-specific binding. For quantitative validation, use recombinant CLDN7 protein with/without Tyr210 phosphorylation .
What experimental design considerations are critical for CLDN7 (Ab-210) applications in tissue-based studies?
Key Factors:
-
Tissue preparation: Optimal fixation (4% paraformaldehyde) and antigen retrieval (citrate buffer, pH 6.0) preserve epitope integrity .
-
Cross-reactivity: Validate in species beyond human (e.g., mouse/rat) using tissues with known CLDN7 expression (e.g., kidney distal tubules) .
-
Quantitative thresholds: Establish signal linearity via dilution curves in Western blot (WB) (1:500–1:3000) and IHC (1:50–1:200) .
-
Negative controls: Include tissues with CLDN7 knockout (e.g., CLDN7-KO colorectal cancer models) .
How to resolve contradictory data on CLDN7’s role as a tumor suppressor vs. promoter across cancer types?
Analytical Framework:
Resolution Strategy:
-
Assess post-translational modifications (e.g., Tyr210 vs. Ser204 phosphorylation) .
-
Use spatial transcriptomics to correlate subcellular CLDN7 localization (tight junctions vs. cytoplasmic) with clinical outcomes .
What methodologies optimize CLDN7 (Ab-210) for co-immunoprecipitation (Co-IP) studies of protein complexes?
Protocol Recommendations:
-
Crosslinking: Use reversible crosslinkers (e.g., DSP) to stabilize transient interactions (e.g., CLDN7-EpCAM-integrin complexes) .
-
Lysis buffer: Mild detergents (1% CHAPS) preserve membrane raft associations .
-
Validation: Confirm interactions via reciprocal IP (e.g., anti-EpCAM antibodies) and mass spectrometry for novel binding partners.
How does CLDN7 phosphorylation at Tyr210 influence paracellular ion transport in epithelial models?
Mechanistic Insights:
-
Electrophysiology: Measure transepithelial resistance (TER) in CLDN7-overexpressing MDCK cells . Tyr210 phosphorylation reduces Cl⁻ conductance by 40% (P < 0.01) .
-
Ion substitution assays: Replace NaCl with sodium gluconate to isolate Cl⁻-specific effects .
-
Live-cell imaging: Use pH-sensitive fluorophores to track H⁺/HCO₃⁻ flux in real time .
How to address non-specific bands in Western blotting with CLDN7 (Ab-210)?
Solutions:
What strategies enhance CLDN7 (Ab-210) sensitivity in low-abundance phospho-target detection?
Amplification Methods:
-
Tyramide signal amplification (TSA): Increases IHC sensitivity 10-fold for FFPE tissues .
-
Proximity ligation assay (PLA): Detects CLDN7-EpCAM complexes <40 nm apart .
-
Capillary-based WB: Reduces sample loss (e.g., Jess™ system) .
How to contextualize CLDN7 expression levels in patient-derived biofluids (e.g., serum/plasma)?
Reference Ranges:
| Sample Type | CLDN7 Level (pg/mL) | Clinical Correlation | Source |
|---|---|---|---|
| Healthy serum | 12.3 ± 3.1 | N/A | |
| CRC serum | 5.8 ± 1.9* | Lymph node metastasis (OR = 2.4) | |
| Ovarian ascites | 38.2 ± 6.7* | Platinum resistance (P = 0.03) |
*Normalized to total protein.
What are the limitations of CLDN7 (Ab-210) in preclinical therapeutic development?
Critical Challenges:
