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Understanding the Role of Therapy-Induced Secretome in Chemo-resistance and EMT in Triple-Negative Breast Cancer
CC BY 4.0 · Indian J Med Paediatr Oncol 2024; 45(S 01): S1-S16
DOI: DOI: 10.1055/s-0044-1788239
*Corresponding author: (e-mail: nandiniverma.cri@gmail.com).
Abstract
Background: Triple-negative breast cancer (TNBC) has worst prognosis amongst various subtypes of breast cancer. Therapy-induced cell secretome is known to promote therapy resistance and tumor progression. Highly secretory nature of TNBC cells makes it important to understand the role of therapy induced TNBC secretome in chemo-resistance and metastasis.
Material and methods: TNBC Proliferating Drug Tolerant Persister (PDTP) cells model was derived by treating TNBC cells with high chemotherapeutic doses, followed by recovery in drug-free medium. PDTPs were characterized, and effects of TNBC PDTP-secretome on parental TNBC cells were checked using techniques like mass spectrometry, MTT, and western blot.
Results: PDTPs have high drug tolerance and lower expression of GPX4 compared to parental cells. Secretome from proliferating drug-tolerant persister cells imparted epithelial to mesenchymal transition (EMT) and drug tolerance in parental TNBC cells. Mass spectrometric analysis of PDTP and parental TNBC cell lysate revealed secretory protein Galectin-1 to be the most differentially overexpressed proteins in PDTP cells. Upon analyzing the clinical data, it was found that the expression of Galectin-1 was significantly higher in the nonresponder cohort of TNBC patients undergoing chemotherapy.
Conclusion: This study showed that TNBC PDTP secretome plays role in providing chemo-tolerance and EMT phenotype to TNBC cells. Also, Galectin-1 may serve as a potential biomarker to understand the prognosis of TNBC patients undergoing chemotherapy.
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
*Corresponding author: (e-mail: nandiniverma.cri@gmail.com).
Abstract
Background: Triple-negative breast cancer (TNBC) has worst prognosis amongst various subtypes of breast cancer. Therapy-induced cell secretome is known to promote therapy resistance and tumor progression. Highly secretory nature of TNBC cells makes it important to understand the role of therapy induced TNBC secretome in chemo-resistance and metastasis.
Material and methods: TNBC Proliferating Drug Tolerant Persister (PDTP) cells model was derived by treating TNBC cells with high chemotherapeutic doses, followed by recovery in drug-free medium. PDTPs were characterized, and effects of TNBC PDTP-secretome on parental TNBC cells were checked using techniques like mass spectrometry, MTT, and western blot.
Results: PDTPs have high drug tolerance and lower expression of GPX4 compared to parental cells. Secretome from proliferating drug-tolerant persister cells imparted epithelial to mesenchymal transition (EMT) and drug tolerance in parental TNBC cells. Mass spectrometric analysis of PDTP and parental TNBC cell lysate revealed secretory protein Galectin-1 to be the most differentially overexpressed proteins in PDTP cells. Upon analyzing the clinical data, it was found that the expression of Galectin-1 was significantly higher in the nonresponder cohort of TNBC patients undergoing chemotherapy.
Conclusion: This study showed that TNBC PDTP secretome plays role in providing chemo-tolerance and EMT phenotype to TNBC cells. Also, Galectin-1 may serve as a potential biomarker to understand the prognosis of TNBC patients undergoing chemotherapy.
No conflict of interest has been declared by the author(s).
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India