Blockage of Squamous Cancer Cell Collective Invasion by FAK Inhibition Is Released by CAFs and MMP-2
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Modulation of Collective Cell Migration by Focal Adhesion Kinase
2.2. Cancer-Associated Fibroblasts Derived from Human SCCs Promote and Lead the Invasive Front of FAK-Deficient SCC Cells in an MMP-2 Independent Mode
2.3. MMP-2 Promotes Collective Cell Invasion and Counteract the Effect of FAK Inhibition
2.4. Cellular Phenotypic Plasticity Associated with FAK Overexpression in SCC Cells
2.5. EMT Plasticity Associated with FAK and MMP-2 Expression
2.6. FAK and MMP-2 mRNA Expression in Head and Neck SCC and Clinicopathologic Variables
3. Discussion
4. Materials and Methods
4.1. Cell Culture, Transfections and Treatments
4.2. Reverse Transcription and qPCR
4.3. Multicellular-Spheres Generation and Migration Analysis
4.4. Immunohistochemistry and Immunofluorescence
4.5. Western Blot
4.6. Time-Lapse and Confocal Reflection Microscopy
4.7. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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PTK2 mRNA Levels | MMP2 mRNA Levels | ||||||
---|---|---|---|---|---|---|---|
N | Low | High | p | Low | High | p | |
pT classification | |||||||
T1–T2 | 209 | 111 | 98 | 0.094 | 124 | 85 | <0.0001 |
T3–T4 | 334 | 152 | 182 | 141 | 193 | ||
pN classification | |||||||
N0 | 193 | 102 | 91 | 0.005 | 105 | 88 | 0.021 |
N+ | 347 | 159 | 188 | 159 | 188 | ||
Distant metastasis | |||||||
M0 | 190 | 96 | 94 | 0.450 | 97 | 93 | 0.192 |
M+ | 66 | 37 | 29 | 39 | 27 | ||
Disease stage | |||||||
I–II | 119 | 67 | 52 | 0.098 | 70 | 49 | 0.007 |
III–IV | 374 | 178 | 196 | 167 | 207 |
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Sáenz-de-Santa-María, I.; Celada, L.; San José Martínez, A.; Cubiella, T.; Chiara, M.-D. Blockage of Squamous Cancer Cell Collective Invasion by FAK Inhibition Is Released by CAFs and MMP-2. Cancers 2020, 12, 3708. https://doi.org/10.3390/cancers12123708
Sáenz-de-Santa-María I, Celada L, San José Martínez A, Cubiella T, Chiara M-D. Blockage of Squamous Cancer Cell Collective Invasion by FAK Inhibition Is Released by CAFs and MMP-2. Cancers. 2020; 12(12):3708. https://doi.org/10.3390/cancers12123708
Chicago/Turabian StyleSáenz-de-Santa-María, Inés, Lucía Celada, Andrés San José Martínez, Tamara Cubiella, and María-Dolores Chiara. 2020. "Blockage of Squamous Cancer Cell Collective Invasion by FAK Inhibition Is Released by CAFs and MMP-2" Cancers 12, no. 12: 3708. https://doi.org/10.3390/cancers12123708