ALCAM: A Novel Surface Marker on EpCAMlow Circulating Tumor Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient-Derived Tumor Cell lines
2.2. Naïve Neutrophil Isolation
2.3. Flow Cytometric Surface Protein Characterization
2.4. Karyotyping
2.5. Preparation of Surface Proteome
2.6. Preparation of Samples for LC-MS
2.7. Transmission Electron Microscopy
2.8. LC-MS/MS Analysis
2.9. Proteome Discoverer Label-Free Quantitation Analysis
2.10. GEMM Animal Experiments
2.11. CTC and DTC Isolation from KPC Mice
2.12. HEK 293 and CTC Cell Line Staining
2.13. CTC Immunostaining and Enumeration
2.14. Enrichment Analyses
2.15. Generation of a Mouse–Human Hybrid TMA
2.16. Histochemical Validation of Selected Markers
3. Results
3.1. CTCs Express Multiple Surface Proteins That Might Play a Role in Pancreatic Cancer
3.2. Variation in Biomarkers on Surface Could Be Attributed to the Genetic Makeup of the CTCs
3.3. CTCs Express Differing Levels of Biomarkers on the Surface When Grown in Different Culture Conditions
3.3.1. CTC Surface Markers Differ in Cells Grown in Adherent or Low Attachment Conditions
3.3.2. CTC Surface Markers Are Differentially Regulated on Exposure to Naïve Neutrophils
3.4. GO Analysis Indicates a Unique Repertoire of Enrichments in Different CTC Culture Conditions
3.5. ALCAM Is a Reliable Marker Expressed in PDAC CTCs
3.6. Alcam Is Expressed in PDAC GEMM Tumors, Distant Metastatic Sites, CTCs, and DTCs
3.7. ALCAM Is Expressed in Diseased Pancreas and Related Metastases and on the Surface of CTCs Isolated from PDAC Patients
3.8. ALCAM Correlates with Multiple Signaling Pathways in Pancreatic Cancer
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Protein Marker | Gene Name | Description | CM61 (% + ve) | CF49 (% + ve) | HM59 (% + ve) | |
---|---|---|---|---|---|---|
1 | CD85H | LILRA2 | Leukocyte Immunoglobulin-Like Receptor Subfamily A member 2 | 99.93 | 100 | 100 |
2 | CD166 | ALCAM | Activated Leukocyte Cell Adhesion Molecule | 99.83 | 99.95 | 99.98 |
3 | MICA/MICB | MICA/MICB | MHC Class I polypeptide-related sequence A/B | 99.90 | 99.93 | 99.86 |
4 | CD9 | CD9 | CD9 antigen | 99.73 | 99.79 | 99.93 |
5 | EPHA2 | EPHA2 | Ephrin Type A receptor 2 | 97.63 | 99.19 | 99.16 |
6 | CD252 | TNFSF4 | Tumor Necrosis Factor Ligand Superfamily member 4 | 93.08 | 95.88 | 97.67 |
7 | CD129 | IL9R | Interleukin-9 Receptor | 90.50 | 94.89 | 93.97 |
8 | CD73 | NT5E | 5′ Nucleotidase | 83.43 | 90.05 | 90.40 |
9 | CD263 | TNFRSF10C | Tumor Necrosis factor receptor superfamily member 10C | 67.75 | 78.85 | 83.37 |
10 | CD215 | IL15RA | Interleukin 15 receptor subunit alpha | 60.04 | 57.96 | 72.92 |
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Signorelli, R.; Giret, T.M.; Umland, O.; Hadisurya, M.; Lavania, S.; Charles Richard, J.L.; Middleton, A.; Boone, M.M.; Ergonul, A.B.; Tao, W.A.; et al. ALCAM: A Novel Surface Marker on EpCAMlow Circulating Tumor Cells. Biomedicines 2022, 10, 1983. https://doi.org/10.3390/biomedicines10081983
Signorelli R, Giret TM, Umland O, Hadisurya M, Lavania S, Charles Richard JL, Middleton A, Boone MM, Ergonul AB, Tao WA, et al. ALCAM: A Novel Surface Marker on EpCAMlow Circulating Tumor Cells. Biomedicines. 2022; 10(8):1983. https://doi.org/10.3390/biomedicines10081983
Chicago/Turabian StyleSignorelli, Rossana, Teresa Maidana Giret, Oliver Umland, Marco Hadisurya, Shweta Lavania, John Lalith Charles Richard, Ashley Middleton, Melinda Minucci Boone, Ayse Burcu Ergonul, Weiguo Andy Tao, and et al. 2022. "ALCAM: A Novel Surface Marker on EpCAMlow Circulating Tumor Cells" Biomedicines 10, no. 8: 1983. https://doi.org/10.3390/biomedicines10081983