Stimulated Expression of CXCL12 in Adrenocortical Carcinoma by the PPARgamma Ligand Rosiglitazone Impairs Cancer Progression
Abstract
:1. Introduction
2. Results
2.1. CXCL12 and Its Cognate Receptors Are Differentially Expressed in ACC and Normal Adrenocortex
2.2. Prognostic Value of CXCL12 Expression in ACC
2.3. Rosiglitazone Upregulates CXCL12 Expression and Downregulates CXCR4/CXCR7 Expression in Adrenocortical Cancer Cells In Vitro and in In Vivo ACC Xenograft Mouse Models
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Antibodies
4.3. Histologic Diagnosis and Immunohistochemistry
4.4. Cell Culture and Growth Analysis
4.5. RNA Isolation and Quantitative Real-Time PCR
4.6. Sodium Dodecyl Sulphate PolyAcrylamide Gel Electrophoresis (SDS-PAGE) and Western Blot Analysis
4.7. Immunofluorescence Confocal Microscopy Analysis of Tissues and Cells
4.8. ACC Mouse Xenograft Models
4.9. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Patients Characteristics | Total Cohort (n = 22) | Low CXCL12 (n = 15) | High CXCL12 (n = 7) | p |
---|---|---|---|---|
Sex: female, n (%) | 17 (77) | 11 (73) | 6 (86) | ns |
Age at diagnosis (ys), mean ± SE | 48.9 ± 3.3 | 53.1 ± 3.8 | 38.3 ± 4.6 | 0.041 |
ENSAT stage, n (%) | 0.05 | |||
I | 3 (14) | 1 (7) | 2 (29) | |
II | 5 (23) | 2 (13) | 3 (43) | |
III | 9 (41) | 8 (53) | 1 (14) | |
IV | 4 (18) | 4 (27) | 0 (0) | |
Unknown | 1 (4) | 0 (0) | 1 (14) | |
Metastasis/Recurrence, n (%) | 13 (59) | 12 (80) | 1 (14) | 0.004 |
no information | 0 (0) | 0 (0) | 0 (0) | |
Death for ACC, n (%) | 9 (41) | 9 (60) | 0 (0) | ns |
no information | 0 (0) | 0 (0) | 0 (0) | |
DFS time (months), median [IQR] | 20 (4.5–85) | 10 (0–34) | 94 (6–146) | 0.039 |
PFS time (months), median [IQR] | 20 (6–85) | 10 (1–34) | 94 (6–146) | 0.047 |
OS time (months), median [IQR] | 51 (23–114) | 42 (23–82) | 108 (6–146) | ns |
Tumor size (cm), mean ± SE | 9.7 ± 1.0 | 11.0 ± 1.1 | 6.3 ± 1.5 | 0.035 |
Hormone secretion, n (%) | ns | |||
Yes | 12 (54) | 9 (60) | 3 (43) | |
Cortisol | 5 (23) | 5 (33) | 0 (0) | |
Sex steroids | 7 (32) | 4 (27) | 3 (32) | |
Mineralcorticoids | 1 (0) | 1 (7) | 0 (0) | |
No | 7 (32) | 5 (40) | 1 (15) | |
Unknown | 3 (14) | 0 (0) | 3 (43) | |
Ki67 LI (%), mean ± SE | 18.1 ± 4.8 | 22.3 ± 6.5 | 10.4 ± 5.5 | ns |
Unknown, n (%) | 2 (9) | 2 (13) | 0 (0) | |
Weiss score, mean ± SE | 5.8 ± 1.8 | 6.7 ± 0.4 | 4.3 ± 0.6 | 0.002 |
Unknown, n (%) | 2 (9) | 2 (13) | 0 (0) | |
Resection status, n (%) | ns | |||
R0 | 11 (50) | 8 (54) | 3 (43) | |
R > 0 | 5 (23) | 5 (33) | 0 (0) | |
Unknown | 6 (27) | 2 (13) | 4 (57) | |
Mitotane, n (%) | 0.005 | |||
Yes | 14 (64) | 13 (87) | 1 (14) | |
No | 6 (27) | 2 (13) | 4 (57) | |
Unknown | 2 (9) | 0 (0) | 2 (29) | |
Other Chemotherapy (EDP), n (%) | ns | |||
Yes | 5 (22) | 5 (33) | 0 (0) | |
No | 15 (68) | 9 (60) | 6 (86) | |
Unknown | 2 (9) | 1 (7) | 1 (14) | |
Radiotherapy, n (%) | ns | |||
Yes | 2 (9) | 2 (9) | 0 (9) | |
No | 18 (91) | 13 (91) | 7 (91) | |
Unknown | 2 (0) | 0 (0) | 0 (0) |
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Cantini, G.; Fei, L.; Canu, L.; Lazzeri, E.; Sottili, M.; Francalanci, M.; Angelotti, M.L.; De Filpo, G.; Ercolino, T.; Gelmini, S.; et al. Stimulated Expression of CXCL12 in Adrenocortical Carcinoma by the PPARgamma Ligand Rosiglitazone Impairs Cancer Progression. J. Pers. Med. 2021, 11, 1097. https://doi.org/10.3390/jpm11111097
Cantini G, Fei L, Canu L, Lazzeri E, Sottili M, Francalanci M, Angelotti ML, De Filpo G, Ercolino T, Gelmini S, et al. Stimulated Expression of CXCL12 in Adrenocortical Carcinoma by the PPARgamma Ligand Rosiglitazone Impairs Cancer Progression. Journal of Personalized Medicine. 2021; 11(11):1097. https://doi.org/10.3390/jpm11111097
Chicago/Turabian StyleCantini, Giulia, Laura Fei, Letizia Canu, Elena Lazzeri, Mariangela Sottili, Michela Francalanci, Maria Lucia Angelotti, Giuseppina De Filpo, Tonino Ercolino, Stefania Gelmini, and et al. 2021. "Stimulated Expression of CXCL12 in Adrenocortical Carcinoma by the PPARgamma Ligand Rosiglitazone Impairs Cancer Progression" Journal of Personalized Medicine 11, no. 11: 1097. https://doi.org/10.3390/jpm11111097