Exploring the Impact of Senescent Stromal Cells on Tumor Cell Stemness
DOI:
https://doi.org/10.47611/jsrhs.v13i4.7580Keywords:
tumor stromal fibroblast, cell senescence, lung cancer, drug resistance, cancer stemnessAbstract
Aging is a great risk factor for cancer. Many types of cancer get more aggressive with aging. Cancer stem cells play a critical role during cancer progression and recurrence, which might enhance aging-associated cancer aggressiveness. At the cellular level, senescent cell accumulation is a main cause of aging. While senescence is traditionally considered a tumor-suppressive mechanism, recent studies suggest that senescent stromal cells may exert paradoxical effects on the stemness properties of adjacent tumor cells.
This study delves into the interplay between tumor stromal cell senescence and the stemness in lung cancer cells. We investigated the impact of senescent MRC5 conditioned medium on tumor cell behavior. Initial experiments revealed that MRC5 stromal lung fibroblast induced a robust senescent state by H2O2 and carboplatin. Subsequent investigations using colony formation assays underscored an augmented clonogenic potential in cells cultured with senescent MRC5 conditioned medium, indicative of heightened tumor cell stemness. Expanding our analysis to drug resistance, we observed a pronounced resistance to carboplatin in tumor cells exposed to senescent MRC5 conditioned medium. To decipher the molecular underpinnings of these phenotypic changes, we quantified the expression of cancer stemness markers, revealing a specific pattern of upregulation.
These findings collectively highlight the impact of senescent stromal cells on tumor cells stemness, indicating a distinctive molecular signature associated with the acquisition of stem-like properties. Understanding these complexities contributes to our knowledge of tumor heterogeneity and may inform novel therapeutic strategies.
Downloads
References or Bibliography
Bisht, S., Nigam, M., Kunjwal, S. S., Sergey, P., Mishra, A. P., & Sharifi-Rad, J. (2022). Cancer Stem Cells: From an Insight into the Basics to Recent Advances and Therapeutic Targeting. Stem Cells International, 2022, 9653244. https://doi.org/10.1155/2022/9653244
Bousset, L., & Gil, J. (2022). Targeting senescence as an anticancer therapy. Molecular Oncology, 16(21), 3855–3880. https://doi.org/10.1002/1878-0261.13312
Di Micco, R., Krizhanovsky, V., Baker, D., & d’Adda di Fagagna, F. (2021). Cellular senescence in ageing: From mechanisms to therapeutic opportunities. Nature Reviews. Molecular Cell Biology, 22(2), 75–95. https://doi.org/10.1038/s41580-020-00314-w
Duan, J., Duan, J., Zhang, Z., & Tong, T. (2005). Irreversible cellular senescence induced by prolonged exposure to H2O2 involves DNA-damage-and-repair genes and telomere shortening. The International Journal of Biochemistry & Cell Biology, 37(7), 1407–1420. https://doi.org/10.1016/j.biocel.2005.01.010
Huang, W., Hickson, L. J., Eirin, A., Kirkland, J. L., & Lerman, L. O. (2022). Cellular senescence: The good, the bad and the unknown. Nature Reviews. Nephrology, 18(10), 611–627. https://doi.org/10.1038/s41581-022-00601-z
Kumari, R., & Jat, P. (2021). Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype. Frontiers in Cell and Developmental Biology, 9, 645593. https://doi.org/10.3389/fcell.2021.645593
Lei, Z.-N., Tian, Q., Teng, Q.-X., Wurpel, J. N. D., Zeng, L., Pan, Y., & Chen, Z.-S. (2023). Understanding and targeting resistance mechanisms in cancer. MedComm, 4(3), e265. https://doi.org/10.1002/mco2.265
Li, Y.-R., Fang, Y., Lyu, Z., Zhu, Y., & Yang, L. (2023). Exploring the dynamic interplay between cancer stem cells and the tumor microenvironment: Implications for novel therapeutic strategies. Journal of Translational Medicine, 21(1), 686. https://doi.org/10.1186/s12967-023-04575-9
Malayaperumal, S., Marotta, F., Kumar, M. M., Somasundaram, I., Ayala, A., Pinto, M. M., Banerjee, A., & Pathak, S. (2023). The Emerging Role of Senotherapy in Cancer: A Comprehensive Review. Clinics and Practice, 13(4), 838–852. https://doi.org/10.3390/clinpract13040076
Marzagalli, M., Fontana, F., Raimondi, M., & Limonta, P. (2021). Cancer Stem Cells-Key Players in Tumor Relapse. Cancers, 13(3), 376. https://doi.org/10.3390/cancers13030376
Mohan, A., Raj Rajan, R., Mohan, G., Kollenchery Puthenveettil, P., & Maliekal, T. T. (2021). Markers and Reporters to Reveal the Hierarchy in Heterogeneous Cancer Stem Cells. Frontiers in Cell and Developmental Biology, 9, 668851. https://doi.org/10.3389/fcell.2021.668851
Nakamura, D. (2023). The evaluation of tumorigenicity and characterization of colonies in a soft agar colony formation assay using polymerase chain reaction. Scientific Reports, 13(1), 5405. https://doi.org/10.1038/s41598-023-32442-6
Phi, L. T. H., Sari, I. N., Yang, Y.-G., Lee, S.-H., Jun, N., Kim, K. S., Lee, Y. K., & Kwon, H. Y. (2018). Cancer Stem Cells (CSCs) in Drug Resistance and their Therapeutic Implications in Cancer Treatment. Stem Cells International, 2018, 5416923. https://doi.org/10.1155/2018/5416923
Quail, D. F., & Joyce, J. A. (2013). Microenvironmental regulation of tumor progression and metastasis. Nature Medicine, 19(11), 1423–1437. https://doi.org/10.1038/nm.3394
Rich, J. N. (2016). Cancer stem cells: Understanding tumor hierarchy and heterogeneity. Medicine, 95(1 Suppl 1), S2–S7. https://doi.org/10.1097/MD.0000000000004764
Rutecki, S., Pakuła-Iwańska, M., Leśniewska-Bocianowska, A., Matuszewska, J., Rychlewski, D., Uruski, P., Stryczyński, Ł., Naumowicz, E., Szubert, S., Tykarski, A., Mikuła-Pietrasik, J., & Książek, K. (2024). Mechanisms of carboplatin- and paclitaxel-dependent induction of premature senescence and pro-cancerogenic conversion of normal peritoneal mesothelium and fibroblasts. The Journal of Pathology, 262(2), 198–211. https://doi.org/10.1002/path.6223
Valieva, Y., Ivanova, E., Fayzullin, A., Kurkov, A., & Igrunkova, A. (2022). Senescence-Associated β-Galactosidase Detection in Pathology. Diagnostics (Basel, Switzerland), 12(10), 2309. https://doi.org/10.3390/diagnostics12102309
Walcher, L., Kistenmacher, A.-K., Suo, H., Kitte, R., Dluczek, S., Strauß, A., Blaudszun, A.-R., Yevsa, T., Fricke, S., & Kossatz-Boehlert, U. (2020). Cancer Stem Cells-Origins and Biomarkers: Perspectives for Targeted Personalized Therapies. Frontiers in Immunology, 11, 1280. https://doi.org/10.3389/fimmu.2020.01280
Xiao, S., Qin, D., Hou, X., Tian, L., Yu, Y., Zhang, R., Lyu, H., Guo, D., Chen, X.-Z., Zhou, C., & Tang, J. (2023). Cellular senescence: A double-edged sword in cancer therapy. Frontiers in Oncology, 13, 1189015. https://doi.org/10.3389/fonc.2023.1189015
Ye, M., Huang, X., Wu, Q., & Liu, F. (2023). Senescent Stromal Cells in the Tumor Microenvironment: Victims or Accomplices? Cancers, 15(7), 1927. https://doi.org/10.3390/cancers15071927
Published
How to Cite
Issue
Section
Copyright (c) 2024 Shiwen Yin; Zhongchi Li
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Copyright holder(s) granted JSR a perpetual, non-exclusive license to distriute & display this article.
