S100A2 Human

What is the molecular structure of human S100A2?

Human S100A2 is a 98 amino acid protein with a molecular weight of approximately 10 kDa. The protein contains two EF-hand motifs (amino acids 13-48 and 51-86) that serve as calcium-binding domains, plus specific binding sites for calcium (aa 64-75) and zinc (aa 17-22). It forms both noncovalent and covalent homodimers, and can assemble into homotetramers under certain conditions. An alternative splice form with a 40 amino acid insertion after Glycine-48 has also been identified .

How does S100A2 function at the cellular level?

S100A2 primarily functions as a calcium sensor and modulator, contributing to cellular calcium signaling pathways. It interacts with other proteins, particularly TPR-containing proteins, to indirectly influence various physiological processes. S100A2 also regulates both calcium and zinc levels within cells. One of its significant functions appears to be tumor suppression, as it increases p53 activity and may play a role in suppressing tumor cell growth .

In which cell types is S100A2 primarily expressed?

S100A2 is expressed in multiple cell types, including keratinocytes, chondrocytes, and bronchial epithelium. This diverse expression pattern suggests tissue-specific functions and regulatory mechanisms. In pathological contexts, altered expression has been observed in various cancer types, including lung cancer and pancreatic cancer .

What are the recommended methods for detecting S100A2 in clinical samples?

For clinical sample analysis, enzyme-linked immunosorbent assay (ELISA) is a well-established method for S100A2 detection. According to research protocols, supernatants from centrifuged samples (1500 × g for 10 min at 4°C) can be stored at −80°C and then examined using ELISA kits. For optimal results, assays should be run in duplicate with a dilution of 1:5. The test sensitivity for S100A2 detection is approximately 0.124 ng/mL, with an assay range of 0.312–20 ng/mL .

How can Western blot be optimized for S100A2 detection?

For effective Western blot detection of S100A2, researchers should use PVDF membranes probed with anti-S100A2 antibodies (such as monoclonal antibody at 2 μg/mL concentration), followed by appropriate HRP-conjugated secondary antibodies. The expected band for S100A2 appears at approximately 10 kDa. For optimal results, the procedure should be conducted under reducing conditions using appropriate immunoblot buffer systems. A431 human epithelial carcinoma cell line lysates have been successfully used as positive controls for S100A2 detection .

What are the best practices for S100A2 recombinant protein preparation?

Recombinant human S100A2 protein can be effectively expressed in Escherichia coli systems. The optimal expression construct should include the amino acid sequence from position 2 to 98. Purification methods should aim for >90% purity, suitable for applications such as SDS-PAGE and mass spectrometry. Proper quality control should verify the expected amino acid sequence and molecular weight. The purified protein can be used for various applications including as a standard for quantitative assays and for functional studies .

How has S100A2 been implicated in lung cancer diagnostics?

S100A2 has shown promise as a diagnostic biomarker for non-small cell lung cancer (NSCLC) patients with malignant pleural effusion (MPE). Studies have demonstrated significantly elevated levels of S100A2 in MPE compared to benign tubercular pleural effusion (TPE). Specifically, the mean level of S100A2 in MPE was measured at 34.4 ± 1.6 ng/mL compared to 11.4 ± 0.9 ng/mL in TPE (P = 0.000). This significant difference highlights the potential diagnostic value of S100A2 in differentiating malignant from benign pleural effusions .

What is the diagnostic accuracy of S100A2 for differentiating MPE from TPE?

Receiver operating characteristic (ROC) curve analysis has demonstrated that S100A2 levels in pleural effusion have substantial diagnostic value. The area under the ROC curve (AUC) for S100A2 in pleural effusion is 0.887, with a specificity of 85.4% at a sensitivity of 76.9% for distinguishing MPE from TPE (cut-off value: 17.646 pg/ml). In comparison, serum S100A2 has a lower diagnostic value with an AUC of 0.709, specificity of 78.1%, and sensitivity of 63.5% (cut-off value: 13.807 pg/ml). These parameters suggest that pleural fluid S100A2 concentration is a more reliable marker than serum levels for MPE detection .

How does S100A2 expression vary throughout cancer progression?

Research has revealed conflicting patterns of S100A2 expression across different cancer stages, leading to the development of a "dual role concept." According to this theory, S100A2 expression is particularly pronounced in both early and advanced stages of lung cancer but decreased in middle stages. This biphasic expression pattern may explain the seemingly contradictory findings regarding S100A2's role in cancer. In advanced stages, such as in patients with malignant pleural effusion, S100A2 shows significant upregulation, consistent with this dual role hypothesis .

What is the relationship between S100A2 and the immune microenvironment in cancer?

Recent research suggests S100A2 may be involved in the immune infiltration process in pancreatic cancer (PC). Studies indicate it might be responsible for maintaining an immune-suppressive status in the PC microenvironment. This finding expands the understanding of S100A2 beyond its role as a calcium-binding protein to include potential immune modulatory functions, which could have significant implications for cancer immunotherapy approaches .

How does S100A2 compare with established lung cancer biomarkers?

When compared with traditional lung cancer biomarkers such as carcinoembryonic antigen (CEA), cytokeratin 19 (CYFRA21-1), and neuron-specific enolase (NSE), S100A2 demonstrates comparable or superior diagnostic value for NSCLC with MPE. While significant differences in serum/PE levels of CEA were observed between MPE and TPE groups (P = 0.001 and 0.002 respectively), the statistical significance was stronger for S100A2 (P = 0.000). For CYFRA211 and NSE, their levels in pleural effusion rather than serum showed diagnostic value for PE caused by primary lung neoplasm (P = 0.001 and P = 0.002, respectively) .

What is the comparative diagnostic value of fluid vs. serum S100A2 measurements?

Analysis of diagnostic metrics reveals that S100A2 levels in pleural effusion provide significantly better diagnostic value than serum measurements. Pleural fluid S100A2 demonstrates an AUC of 0.887 with a specificity of 85.4% and sensitivity of 76.9%, whereas serum S100A2 shows a lower AUC of 0.709 with a specificity of 78.1% and sensitivity of 63.5%. This suggests that direct measurement of S100A2 in the affected tissue microenvironment (pleural fluid) offers superior diagnostic performance compared to systemic (serum) measurements .

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What are the key challenges in standardizing S100A2 as a clinical biomarker?

While S100A2 shows promise as a diagnostic biomarker, several challenges must be addressed before clinical implementation. These include: (1) validation with larger sample populations to confirm diagnostic accuracy; (2) standardization of detection methods across laboratories; (3) establishment of universal cut-off values for different clinical contexts; (4) investigation of potential confounding factors that might affect S100A2 levels independent of malignancy; and (5) elucidation of the precise biological mechanisms through which S100A2 contributes to cancer development and progression .

How should researchers approach the contradictory findings regarding S100A2's role in cancer?

The apparent contradictions in S100A2 research findings can be addressed through several methodological approaches: (1) implementing stage-specific analyses that account for the "dual role concept" of biphasic expression; (2) conducting comparative studies across multiple cancer types to identify tissue-specific patterns; (3) performing mechanistic studies that investigate the regulatory pathways controlling S100A2 expression; (4) examining the interaction between S100A2 and other tumor markers or genetic factors; and (5) utilizing multi-omics approaches to place S100A2 within broader molecular networks .

What future research directions should be prioritized for S100A2?

Future research should focus on: (1) large-scale validation studies to confirm S100A2's diagnostic value across diverse patient populations; (2) mechanistic investigations into how S100A2 interacts with the p53 pathway to regulate tumor suppression; (3) exploration of S100A2's role in immune modulation within the tumor microenvironment; (4) development of therapeutic approaches targeting S100A2 or its associated pathways; and (5) longitudinal studies to evaluate S100A2 as a prognostic marker for treatment response and disease progression .