Colorectal Cancer Stem Cells Fuse with Monocytes to Form Tumour Hybrid Cells with the Ability to Migrate and Evade the Immune System
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients and Healthy Volunteers Recruitment
2.2. Cell Culture
2.3. Reverse-Transcription qPCR
2.4. Vital Colorant Assay
2.5. Cell Sorting and Flow Cytometry
2.6. In Vitro Modulation of Monocyte Polarisation
2.7. Soluble Cytokines Quantification
2.8. Transwell Migration Assay
2.9. In Vitro Proliferation Assays
2.10. Soluble Immune-Checkpoint Measurement
2.11. Tissue Sample Immunohistochemistry
2.12. Statistical Analysis
2.13. Ethics Approval
3. Results
3.1. Co-Culture of Colorectal Cancer Stem Cells with Human Monocytes in Vitro Yields a New Hybrid Entity
3.2. Anti-Inflammatory Phenotype Favours THC Generation
3.3. Colorectal THCs Exhibit a High Rate of Migration and Proliferation In Vitro
3.4. Colorectal THCs Inhibit Lymphocyte Proliferation through SIGLEC5 Immune Checkpoint
3.5. THC-Specific Signature Is Present in Primary Tissue and Metastatic Samples of Colorectal Cancer Patients
3.6. THC-Specific Signature Is Present in Circulation of Colorectal Cancer Patients
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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Characteristic | All Patients N = 23 | Stage I N = 4 | Stage II N = 11 | Stage III N = 8 | p-Value |
---|---|---|---|---|---|
Sex | |||||
Male | 14 (61) | 2 (14) | 7 (50) | 5 (36) | 0.438 |
Female | 9 (39) | 2 (22) | 4 (44) | 3 (34) | 0.986 |
Age | |||||
Median Range | 78 (63–92) | 78.5 (63–81) | 78 (68–87) | 73.5 (64–92) | 0.525 |
Metastasis | |||||
Synchronous | 0 (0) | 0 (0) | 0 (0) | 0 (0) | |
Metachronous | 3 (13) | 0 (0) | 0 (0) | 3 (100) | 0.039 |
Exitus | 2 (9) | 0 (0) | 1 (50) | 1 (50) | 0.767 |
Tumour Site | |||||
Ascending Colon | 7 (31) | 1 (14) | 4 (57) | 2 (29) | 0.839 |
Transverse Colon | 4 (17) | 1 (25) | 3 (75) | 0 (0) | 0.273 |
Descending Colon | 4 (17) | 1 (25) | 1 (25) | 2 (50) | 0.603 |
Caecum | 8 (35) | 1 (12) | 3 (38) | 4 (50) | 0.532 |
Comorbidities | |||||
Smoker | 4 (17) | 0 (0) | 3 (75) | 1 (25) | 0.422 |
Arterial Hypertension | 8 (35) | 3 (38) | 4 (50) | 1 (12) | 0.099 |
Dyslipidaemia | 9 (39) | 2 (22) | 6 (67) | 1 (11) | 0.159 |
Diabetes Mellitus | 3 (13) | 2 (66) | 1 (34) | 0 (0) | 0.045 * |
BMI Median Range | 28.3 (23.2–35.5) | 28.4 (26.1–30.8) | 27.1 (23.2–35.4) | 29.7 (23.5–35.5) | 0.919 |
Characteristic | Healthy Volunteers N = 12 | All Patients N = 38 | Stage I N = 10 | Stage II N = 10 | Stage III N = 16 | Stage IV N = 2 | p-Value |
---|---|---|---|---|---|---|---|
Sex | |||||||
Male | 8 (67) | 27(71) | 8 (30) | 8 (30) | 9 (33) | 2 (7) | 0.347 |
Female | 4 (33) | 11 (29) | 2 (18) | 2 (18) | 7 (64) | 0 (0) | 0.500 |
Age | |||||||
Median Range | 44.5 (26–75) | 71.5 (50–92) | 64.5 (62–71) | 72 (50–85) | 75 (50–92) | 68 (55–81) | 0.298 |
Metastasis | |||||||
Synchronous | 2 (5) | 0 (0) | 0 (0) | 0 (0) | 2 (100) | <0.0001 **** | |
Metachronous | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | ||
Exitus | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | ||
Tumour Site | |||||||
Ascending Colon | 11 (30) | 2 (19) | 4 (36) | 4 (36) | 1 (9) | 0.609 | |
Transverse Colon | 2 (5) | 2 (100) | 0 (0) | 0 (0) | 0 (0) | 0.116 | |
Descending Colon | 20 (54) | 4 (20) | 5 (25) | 11 (55) | 0 (0) | 0.207 | |
Caecum | 4 (11) | 2 (50) | 1 (25) | 0 (0) | 1 (25) | 0.104 | |
Comorbidities | |||||||
Smoker | 15 (39) | 4 (27) | 4 (27) | 5 (33) | 2 (13) | 0.317 | |
Arterial Hypertension | 18 (47) | 3 (17) | 5 (27) | 9 (50) | 1 (6) | 0.626 | |
Dyslipidaemia | 11 (29) | 3 (27) | 4 (37) | 3 (27) | 1 (9) | 0.606 | |
Diabetes Mellitus | 8 (21) | 3 (37) | 3 (37) | 1 (13) | 1 (13) | 0.252 | |
BMI Median Range | 27.02 (19.7–42.2) | 27.86 (19.7 31.6) | 26.09 (23.8–33.9) | 26.65 (21.4–42.2) | 25.04 (20.3–29.7) |
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Montalbán-Hernández, K.; Cantero-Cid, R.; Casalvilla-Dueñas, J.C.; Avendaño-Ortiz, J.; Marín, E.; Lozano-Rodríguez, R.; Terrón-Arcos, V.; Vicario-Bravo, M.; Marcano, C.; Saavedra-Ambrosy, J.; et al. Colorectal Cancer Stem Cells Fuse with Monocytes to Form Tumour Hybrid Cells with the Ability to Migrate and Evade the Immune System. Cancers 2022, 14, 3445. https://doi.org/10.3390/cancers14143445
Montalbán-Hernández K, Cantero-Cid R, Casalvilla-Dueñas JC, Avendaño-Ortiz J, Marín E, Lozano-Rodríguez R, Terrón-Arcos V, Vicario-Bravo M, Marcano C, Saavedra-Ambrosy J, et al. Colorectal Cancer Stem Cells Fuse with Monocytes to Form Tumour Hybrid Cells with the Ability to Migrate and Evade the Immune System. Cancers. 2022; 14(14):3445. https://doi.org/10.3390/cancers14143445
Chicago/Turabian StyleMontalbán-Hernández, Karla, Ramón Cantero-Cid, José Carlos Casalvilla-Dueñas, José Avendaño-Ortiz, Elvira Marín, Roberto Lozano-Rodríguez, Verónica Terrón-Arcos, Marina Vicario-Bravo, Cristóbal Marcano, Jorge Saavedra-Ambrosy, and et al. 2022. "Colorectal Cancer Stem Cells Fuse with Monocytes to Form Tumour Hybrid Cells with the Ability to Migrate and Evade the Immune System" Cancers 14, no. 14: 3445. https://doi.org/10.3390/cancers14143445