Dual Targeting of Stromal Cell Support and Leukemic Cell Growth by a Peptidic PKC Inhibitor Shows Effectiveness against B-ALL
Abstract
:1. Introduction
2. Results
2.1. Cell Growth Inhibition of Leukemic Cell Lines by HKPS
2.2. Cell Growth Inhibition of Leukemic Cells from B-ALL Patients by HKPS
2.3. Cell Growth Inhibition of B-ALL Cells by HKPS in a Co-Culture System with MSC
2.4. Differential Cytotoxicity Evaluation of HKPS in MSC and Leukemic Cells
2.5. Role of PKC Inhibition in Cell Adhesion between MSC and B-ALL Cells
2.6. Role of Soluble Factors and Cell–Cell Interactions in MSC Protection
2.7. Adhesion Molecules Involved in MSC and Leukemic Cell Interactions
2.8. HKPS Sensitization of MSC to Dexamethasone Treatment
3. Discussion
4. Materials and Methods
4.1. BM-MSC Isolation (Stromal Cell Support)
4.2. Immunophenotypic and Multipotent Differentiation Capacity in BM-MSC
4.3. Immortalized Leukemic Cell Lines
4.4. Patient B-ALL Cells Isolation and Characterization
4.5. Establishment of the Co-Cultures of Leukemic Cells with MSC
4.6. Peptide Synthesis and Characterization
4.7. Cytotoxicity of Leukemic Cells Induced by PKC Inhibitors
4.8. Differential Cytotoxicity in MSC and Leukemic Cells Determined by Flow Cytometry
4.9. Functional Cell Adhesion Assay of Leukemic Cells
4.10. Contribution of Soluble Factors vs. Direct Cell Contact to the MSC Support
4.10.1. Conditioned Media Evaluation
4.10.2. TW Assay Evaluation
4.11. Expression of Adhesion Molecules in MSC and B-ALL Cells
4.12. Treatment with Cytotoxic Agents
4.13. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
MSC | Mesenchymal stem cells |
PKC | Protein kinase C |
B-ALL | B-cell acute lymphoblastic leukaemia |
CLL | Chronic lymphoid leukaemia |
AML | Acute myeloid leukaemia |
BM | Bone Marrow |
MNC | Mononuclear cells |
FBS | Fetal bovine serum |
STAU | Staurosporine |
ENZA | Enzastaurine |
DEXA | Dexamethasone |
NT | Non treated |
TW | Transwell |
MRD | Minimal residual disease |
VCAM-1 | Vascular cell-adhesion molecule-1 |
VLA | Very late antigen |
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Ruiz-Aparicio, P.F.; Vanegas, N.-D.P.; Uribe, G.I.; Ortiz-Montero, P.; Cadavid-Cortés, C.; Lagos, J.; Flechas-Afanador, J.; Linares-Ballesteros, A.; Vernot, J.-P. Dual Targeting of Stromal Cell Support and Leukemic Cell Growth by a Peptidic PKC Inhibitor Shows Effectiveness against B-ALL. Int. J. Mol. Sci. 2020, 21, 3705. https://doi.org/10.3390/ijms21103705
Ruiz-Aparicio PF, Vanegas N-DP, Uribe GI, Ortiz-Montero P, Cadavid-Cortés C, Lagos J, Flechas-Afanador J, Linares-Ballesteros A, Vernot J-P. Dual Targeting of Stromal Cell Support and Leukemic Cell Growth by a Peptidic PKC Inhibitor Shows Effectiveness against B-ALL. International Journal of Molecular Sciences. 2020; 21(10):3705. https://doi.org/10.3390/ijms21103705
Chicago/Turabian StyleRuiz-Aparicio, Paola Fernanda, Natalia-Del Pilar Vanegas, Gloria Inés Uribe, Paola Ortiz-Montero, Camila Cadavid-Cortés, Jimmy Lagos, Jessica Flechas-Afanador, Adriana Linares-Ballesteros, and Jean-Paul Vernot. 2020. "Dual Targeting of Stromal Cell Support and Leukemic Cell Growth by a Peptidic PKC Inhibitor Shows Effectiveness against B-ALL" International Journal of Molecular Sciences 21, no. 10: 3705. https://doi.org/10.3390/ijms21103705