Abstract 28P
Background
Early diagnosis of cancer is imperative to stop the spreading of the disease and for the long-term survival of the patients. Focus on detecting symptomatic patients as early as possible gives the best opportunity for successful treatment. But the failure to detect the rare cancer stem cells (CSCs) population that uniquely initiates and sustains the disease poses a major challenge to early tumor detection. Recent reports indicate the contribution of exosomes, secreted by CSCs to orchestrate the formation and maintenance of tumor-promoting microenvironment.
Methods
Breast CSCs (bCSCs) were purified from breast cancer cell lines and human breast tumor tissues following which CSC-derived exosomes (CDEs) were isolated. CDEs were isolated from the tumor blood samples and characterized through DLS, AFM, and western blot analysis. CDE-FOXP3 was detected through flow cytometry, western blot, and mass spectrometry analysis.
Results
We observed a higher level of FOXP3 expression in MDA-MB-468 CSC-derived exosomes (CDEs) as compared to exosomes isolated from non-tumorigenic MCF10A derived stem cells. Interestingly CDEs isolated from tumor patients also showed a comparable FOXP3 expression. A strong positive correlation between CSC percentage and CDE-FOXP3 expression in tumor patients was also observed. Furthermore, we report significant elevation of CDE-FOXP3 in peripheral blood of 18 clinically diagnosed breast cancer patients compared to 19 healthy individuals in a randomized, open-label, case-control study. The clearly detectable non-overlapping ranges of CDE-FOXP3 in breast cancer patients and healthy cohorts highlight the potential of CDE-FOXP3 to be a low-cost blood-based detection marker eligible for a phase-I clinical study.
Conclusions
Detection of CDE-FOXP3 in the peripheral blood of breast cancer patients will allow us to detect CSCs in a non-invasive method. Its expression is distinguishable from healthy donors due to clearly definable ranges and remains unchanged even during chemotherapy, suggesting future prospects of the same in the application as an early diagnostic marker. Collectively our data demonstrate that detecting CDE-FOXP3 can become a quick non-invasive way to diagnose and screen early-stage breast cancer in a cost-effective manner.
Clinical trial identification
Editorial acknowledgement
We sincerely thank Dr. Debomita Sengupta for the editorial assistance provided to us.
Legal entity responsible for the study
The authors.
Funding
Council of Scientific and Industrial Research, Govt of India.
Disclosure
All authors have declared no conflicts of interest.