Pathological and Oncological Sciences I.
Vajda, Flóra
U5UOHT
HUN-REN Research Centre for Natural Sciences
06303617870
vajdaflo@gmail.com
Role of Mesenchymal Stem Cells in Cancer Cell Survivor and Drug Resistance
Flóra Vajda1
1: HUN-REN Research Centre for Natural Sciences
Szóbeli
Pathological and Oncological Sciences I.
Hungarian
Pathological and Oncological Sciences
Mesenchymal stem cells (MSCs) play crucial roles in the complex milieu of the tumor microenvironment (TME), influencing tumorigenesis, invasion, and responses to therapy. While MSCs are known to exhibit both anti-and pro-tumorigenic effects, their sensitivity to chemotherapeutics remains underexplored. The prevailing notion of MSCs possessing greater drug tolerance due to their slower proliferation rate is challenged by our investigation into their responses to nine diverse chemotherapy agents. Despite their slower cell cycle, MSCs show sensitivity to various drugs, albeit with distinct outcomes compared to cancer cells.
Our study reveals that, although MSCs exhibit a similar sensitivity profile to a range of compounds as cancer cells, they suffer less DNA double-stranded breaks and resist apoptosis following treatment. This contradiction in cellular fates after chemotherapy suggests a divergence in response mechanisms between MSCs and cancer cells, impacting treatment efficacy. These findings suggest the importance of considering the differential drug responses of MSCs and cancer cells when designing therapeutic strategies targeting both cell populations.
Furthermore, the dynamic interplay between MSCs and cancer cells adds another level of complexity to their roles in tumor progression and therapy. While the exact impact of MSCs on drug resistance and tumor behavior remains debated, our investigation using 2D co-cultures and 3D co-culture spheroids provides insights into the intricate relationships between these cell types. By creating co-cultures of GFP-expressing MSCs and mCherry-tagged A431 epidermoid carcinoma cells, we elucidated the effects of MSCs on cancer cell growth, survival, and drug sensitivity.
In our experiments, 2D co-cultures did not significantly alter proliferation or drug sensitivity, and slightly changed cytokine secretion in co-culture. However, the 3D co-culture spheroids showed a specific architecture, A431 cells covered MSCs, enhancing cancer cell survival and resistance. This structural arrangement highlights the critical role of physical proximity and cell-cell interactions in mediating the impact of MSCs on cancer cells. These findings pave the way for novel therapeutic approaches that consider the intricate interplay between MSCs and cancer cells in the TME, offering new insights into personalized cancer treatment strategies.
Semmelweis University
Dr. Szakács Gergely, Dr. Füredi András
I do not give consent to the publication of my abstract on the website of the congress.
Szabad
elfogadva
szóbeli
nem rendelkezett róla
8250
12:15
12:25