Exosomes Derived from Metastatic Colon Cancer Cells Induced Oncogenic Transformation and Migratory Potential of Immortalized Human Cells
DOI:
https://doi.org/10.52756/ijerr.2023.v36.003Keywords:
Cancer stemness, exosomes, EMT, HEK, metastasis, SW620Abstract
Tiny vesicles, synthesized from cell membranes through endocytosis, form multivesicular bodies (MVBs). These MVBs can either undergo lysosomal degradation or be released to the extracellular environment. The vesicle that ranges in size from 30-300 nm that were positive for markers such as CD63 or CD9 are known as exosomes. Exosomes are shown to contain various biological macromolecules such as DNA, RNA, miRNA, proteins, and lipids. Releasing exosomes from cells to the extracellular environment is an important strategy to transfer information between the cells. Exosomes from primary colon cancer cells have been shown to induce the oncogenic transformation of normal cells. In this study, we have demonstrated that treating normal cells (HEK) with exosomes derived from the metastatic colon cancer cell line (SW620) increases cell proliferation, allowing the normal cells to grow anchored independently, suggesting the oncogenic transformation of normal cells. In addition, there was an increase in migration and invasion properties of HEK cells exposed to exosomes from SW620 cells. Our results suggest that following the treatment with metastatic colon cancer cell-derived exosomes, the HEK cells underwent an oncogenic transformation and Epithelial-Mesenchymal Transition (EMT) that will allow the cancerous cells to metastasize.
References
Abdouh, M., Zhou, S., Arena, V., Arena, M., Lazaris, A., Onerheim, R., Metrakos, P., & Arena, G. O. (2014). Transfer of malignant trait to immortalized human cells following exposure to human cancer serum. In Journal of Experimental and Clinical Cancer Research, 33, 86. https://doi.org/10.1186/s13046-
-0086-5
Bebelman, M. P., Smit, M. J., Pegtel, D. M., & Baglio, S. R. (2018). Biogenesis and function of extracellular vesicles in cancer. In Pharmacology and Therapeutics, 88, 1-11. https://doi.org/10.1016/j.pharmthera.2018.02.013
Becker, A., Thakur, B. K., Weiss, J. M., Kim, H. S., Peinado, H., & Lyden, D. (2016). Extracellular Vesicles in Cancer: Cell-to-Cell Mediators of Metastasis. Cancer Cell, 30(6), 836-848. https://doi.org/10.1016/j.ccell.2016.10.009
Bidarra, D., Constâncio, V., Barros-Silva, D., Ramalho- Carvalho, J., Moreira-Barbosa, C., Antunes, L., Maurício, J., Oliveira, J., Henrique, R., & Jerónimo, C. (2019). Circulating MicroRNAs as Biomarkers for Prostate Cancer Detection and Metastasis Development Prediction. Frontiers in Oncology, 9, 900. https://doi.org/10.3389/fonc.2019.00900
Bigagli, E., Luceri, C., Guasti, D., & Cinci, L. (2016). Exosomes secreted from human colon cancer cells influence the adhesion of neighboring metastatic cells: Role of microRNA-210. Cancer Biology and Therapy, 17(10), 1062-1069. https://doi.org/10.1080/15384047.2016.1219815
Dai Jie, & Yiqun Jiang. (2020). Exosomes: key players in cancer and potential therapeutic strategy. Nature, 5, 145. https://doi.org/10.1038/s41392-020-00261-0
Das, J., Das, M., Doke, M., Wnuk, S., Stiffin, R., Ruiz, M., & Celli, J. (2021). A small molecule inhibits pancreatic cancer stem cells. International Journal of Experimental Research and Review, 26, 1-15. https://doi.org/10.52756/ijerr.2021.v26.001
Dong, P., Wang, Y., Liu, Y., Zhu, C., Lin, J., Qian, R., Hua, L., & Lu, C. (2022). BMAL1 induces colorectal cancer metastasis by stimulating exosome secretion. Molecular Biology Reports, 49(1). https://doi.org/10.1007/s11033-021-06883-z
Fu, S., Wang, Y., Xia, X., & Zheng, J. C. (2020). Exosome engineering: Current progress in cargo loading and targeted delivery. In NanoImpact, 20, 100261. https://doi.org/10.1016/j.impact.2020.100261
Gilligan, K. E., & Dwyer, R. M. (2017). Engineering Exosomes for Cancer Therapy. International Journal of Molecular Sciences, 18(6), 1122. https://doi.org/10.3390/IJMS18061122
Guo, W., Gao, Y., Li, N., Shao, F., Wang, C., Wang, P., Yang, Z., Li, R., & He, J. (2017). Exosomes: New players in cancer (Review). In Oncology Reports, 38(2), 665-675. https://doi.org/10.3892/or.2017.5714
Huang, T., Sato, Y., Kuramochi, A., Ohba, Y., Sano, M., Miyagishi, M., Tateno, H., Wadhwa, R., Kawasaki, K., Uchida, T., Ekdahl, K. N., Nilsson, B., Chung, U. il, & Teramura, Y. (2023). Surface modulation of extracellular vesicles with cell-penetrating peptide-conjugated lipids for improvement of intracellular delivery to endothelial cells. Regenerative Therapy, 22. https://doi.org/10.1016/j.reth.2022.12.007
Jiang, J., Li, J., Zhou, X., Zhao, X., Huang, B., & Qin, Y. (2022). Exosomes Regulate the Epithelial–Mesenchymal Transition in Cancer. In Frontiers in Oncology, 12. https://doi.org/10.3389/fonc.2022.864980
Kalluri, R., & Weinberg, R. A. (2009). The basics of epithelial-mesenchymal transition. In Journal of Clinical Investigation, 119(6), 1420-1428. https://doi.org/10.1172/JCI39104
Kamerkar, S., LeBleu, V. S., Sugimoto, H., Yang, S., Ruivo, C. F., Melo, S. A., Lee, J. J., & Kalluri, R. (2017). Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature, 546(7659), 498–503. https://doi.org/10.1038/nature22341
Kim, H., Lee, S., Shin, E., Seong, K. M., Jin, Y. W., Youn, H. S., & Youn, B. H. (2020). The Emerging Roles of Exosomes as EMT Regulators in Cancer. Cells, 9(4). 861. https://doi.org/10.3390/cells9040861
Kim, M.S., Haney, M.J., Zhao, Y., Mahajan, V., Deygen, I., Klyachko, N.L., Inskoe, E., Piroyan, A., Sokolsky, M., Okolie, O., Hingtgen, S.D., Kabanov, A.V., & Batrakova, E.V. (2016). Development of exosome- encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine : Nanotechnology, Biology and Medicine, 12(3), 655–664. https://doi.org/10.1016/J.NANO.2015.10.012
Li, P., Liu, X., Xing, W., Qiu, H., Li, R., Liu, S., & Sun, H. (2022). Exosome-derived miR-200a promotes esophageal cancer cell proliferation and migration via the mediating Keap1 expression. Molecular and Cellular Biochemistry, 477(4). https://doi.org/10.1007/s11010-022-04353-z
Lobos-González, L., Bustos, R., Campos, A., Silva, V., Silva, V., Jeldes, E., Salomon, C., Varas-Godoy, M., Cáceres-Verschae, A., Duran, E., Vera, T., Ezquer, F., Ezquer, M., Burzio, V. A., & Villegas, J. (2020). Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells. Scientific Reports, 10, 343. https://doi.org/10.1038/s41598-019-57018-1
Manish, Dash, Palaniyandi Kanakaraj, Ramalingam Satish, S, Sahaabudeen, & N. Sella R. (2021). Exosomes isolated from two different cell lines using three different isolation techniques show variation in physical and molecular characteristics. Biochimica et Biophysica Acta. Biomembranes, 1863(2). https://doi.org/10.1016/J.BBAMEM.2020.183490
Martins, T. S., Catita, J., Rosa, I. M., Da Cruz e Silva, O. A. B., & Henriques, A. G. (2018). Exosome isolation from distinct biofluids using precipitation and column-based approaches. PLoS ONE, 13(6). https://doi.org/10.1371/journal.pone.0198820
Marzagalli, M., Fontana, F., Raimondi, M., & Limonta, P. (2021). Cancer stem cells—key players in tumour relapse. In Cancers, 13, 3. https://doi.org/10.3390/cancers13030376
Mashouri, L., Yousefi, H., Aref, A. R., Ahadi, A. M., Molaei, F., & Alahari, S. K. (2019). Exosomes: Composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Molecular Cancer, 18, 75. https://doi.org/10.1186/s12943-019-0991-5
Nam, G. H., Choi, Y., Kim, G. B., Kim, S., Kim, S. A., & Kim, I. S. (2020). Emerging Prospects of Exosomes for Cancer Treatment: From Conventional Therapy to Immunotherapy. In Advanced Materials, 32(51). https://doi.org/10.1002/adma.202002440
Park, S. Y., Shin, J. H., & Kee, S. H. (2017). E-cadherin expression increases cell proliferation by regulating energy metabolism through nuclear factor-κB in AGS cells. Cancer Science, 108(9). https://doi.org/10.1111/cas.13321
Pinky, Gupta, S., Krishnakumar, V., Sharma, Y., Dinda, A. K., & Mohanty, S. (2021). Mesenchymal Stem Cell Derived Exosomes: a Nano Platform for Therapeutics and Drug Delivery in Combating COVID-19. In Stem Cell Reviews and Reports, https://doi.org/10.1007/s12015-020-10002-z
Rajagopal, C., & Harikumar, K. B. (2018). The origin and functions of exosomes in cancer. In Frontiers in Oncology, 8, 2018. https://doi.org/10.3389/fonc.2018.00066
Risha, Y., Minic, Z., Ghobadloo, S. M., & Berezovski, M.V. (2020). The proteomic analysis of breast cell line exosomes reveals disease patterns and potential biomarkers. Scientific Reports, 10, 13572. https://doi.org/10.1038/s41598-020-70393-4
Sahebi, R., Langari, H., Fathinezhad, Z., Bahari Sani, Z., Avan, A., Ghayour Mobarhan, M., & Rezayi, M. (2020). Exosomes: New insights into cancer mechanisms. In Journal of Cellular Biochemistry, 121, 1. https://doi.org/10.1002/jcb.29120
Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71(3). https://doi.org/10.3322/caac.21660
Thakur, A., Parra, D. C., Motallebnejad, P., Brocchi, M., & Chen, H. J. (2022). Exosomes: Small vesicles with big roles in cancer, vaccine development, and therapeutics. In Bioactive Materials, 10, 281-294. https://doi.org/10.1016/j.bioactmat.2021.08.029
Tsukamoto, M., Iinuma, H., Yagi, T., Matsuda, K., & Hashiguchi, Y. (2017). Circulating Exosomal MicroRNA-21 as a Biomarker in Each Tumor Stage of Colorectal Cancer. Oncology (Switzerland), 92(6), 360–370. https://doi.org/10.1159/000463387
Vakhshiteh, F., Atyabi, F., & Ostad, S. N. (2019). Mesenchymal stem cell exosomes: A two-edged sword in cancer therapy. International Journal of Nanomedicine, 2019(14), 2847—2859. https://doi.org/10.2147/IJN.S200036
Visan, K. S., Lobb, R. J., & Moller, A. (2020). The role of exosomes in the promotion of epithelial-to- mesenchymal transition and metastasis. In Frontiers in Bioscience - Landmark, 25(6), 1022–1057. https://doi.org/10.2741/4846
Wang, B., Wang, Y., Yan, Z., Sun, Y., & Su, C. (2019). Colorectal cancer cell-derived exosomes promote proliferation and decrease apoptosis by activating the ERK pathway. International Journal of Clinical and Experimental Pathology, 12(7).
Wang, X., Tian, L., Lu, J., & Ng, I. O. L. (2022). Exosomes and cancer - Diagnostic and prognostic biomarkers and therapeutic vehicle. In Oncogenesis, 11, 54. https://doi.org/10.1038/s41389-022-00431-5
Yang, B., Feng, X., Liu, H., Tong, R., Wu, J., Li, C., Yu, H., Chen, Y., Cheng, Q., Chen, J., Cai, X., Wu, W.,
Lu, Y., Hu, J., Liang, K., Lv, Z., Wu, J., & Zheng, S. (2020). High-metastatic cancer cells derived exosomal miR92a-3p promotes epithelial- mesenchymal transition and metastasis of low- metastatic cancer cells by regulating PTEN/Akt pathway in hepatocellular carcinoma. Oncogene, 39, 6529–6543. https://doi.org/10.1038/s41388-020-01450-5
Yasodha, K., Lizha Mary, L., Surajit, P., & Satish, R. (2023). Exosomes from metastatic colon cancer cells drive the proliferation and migration of primary colon cancer through increased expression of cancer stem cell markers CD133 and DCLK1. Tissue and Cell, 84, 102163. https://doi.org/10.1016/J.TICE.2023.102163
Zhong, Y., Li, H., Li, P., Chen, Y., Zhang, M., Yuan, Z., Zhang, Y., Xu, Z., Luo, G., Fang, Y., & Li, X. (2021). Exosomes: A New Pathway for Cancer Drug Resistance. In Frontiers in Oncology, 11, 2021. https://doi.org/10.3389/fonc.2021.743556
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