Menu
Home Explore People Places Arts History Plants & Animals Science Life & Culture Technology
On this page
Cancer exodus hypothesis

The cancer exodus hypothesis establishes that circulating tumor cell clusters (CTC clusters) maintain their multicellular structure throughout the metastatic process. It was previously thought that these clusters must dissociate into single cells during metastasis. According to the hypothesis, CTC clusters intravasate (enter the bloodstream), travel through circulation as a cohesive unit, and extravasate (exit the bloodstream) at distant sites without disaggregating, significantly enhancing their metastatic potential. This concept is considered a key advancement in understanding of cancer biology and CTCs role in cancer metastasis.

We don't have any images related to Cancer exodus hypothesis yet.
We don't have any YouTube videos related to Cancer exodus hypothesis yet.
We don't have any PDF documents related to Cancer exodus hypothesis yet.
We don't have any Books related to Cancer exodus hypothesis yet.
We don't have any archived web articles related to Cancer exodus hypothesis yet.

Mechanism

Traditionally, it was believed that CTC clusters needed to dissociate into individual cells during their journey through the bloodstream to seed secondary tumors. However, recent studies show that CTC clusters can travel through the bloodstream intact, enabling them to perform every step of metastasis while maintaining their group/cluster structure.456

The cancer exodus hypothesis asserts that CTC clusters have several distinct advantages that increase their metastatic potential:

  • Higher metastatic efficiency: CTC clusters have been shown to possess superior seeding capabilities at distant sites compared to single CTCs.78
  • Survival and proliferation: The collective nature of CTC clusters allows them to share resources and offer intercellular support, improving their overall survival rates in the bloodstream.910
  • Resistance to treatment: CTC clusters exhibit unique gene expression profiles that contribute to their ability to evade certain cancer therapies, making them more resistant than individual tumor cells.1112

Clinical relevance

The cancer exodus hypothesis offers important insights into how metastasis occurs and highlights the significance of CTC clusters in cancer progression. Detecting and analyzing CTC clusters through liquid biopsies could offer valuable information about the aggressiveness and metastatic potential of cancers.1314 This information is particularly useful for identifying patients who may benefit from more aggressive treatment strategies.1516

Characterization

The hypothesis was developed due to several key studies, which have demonstrated the ability of CTC clusters to:

  • Intravasate and travel as clusters: Research has shown that CTC clusters can enter the bloodstream as a group, travel through the circulatory system intact, and maintain their cluster phenotype during transit.171819
  • Extravasate through angiopellosis: A key finding of the hypothesis is that CTC clusters do not need to disaggregate to exit the bloodstream. Instead, they can undergo a process called angiopellosis, in which entire clusters migrate out of the blood vessels as a group, retaining their multicellular form. 2021

These findings underscore the critical role of CTC clusters in driving the metastatic cascade and suggest that CTC clusters could serve as important biomarkers in cancer diagnosis, prognosis, and treatment planning.22 Additionally, understanding the mechanisms that allow CTC clusters to retain their structure and survive in circulation opens new avenues for targeted cancer therapies designed to disrupt this process.23

Future directions

As research into the cancer exodus hypothesis progresses, new therapeutic strategies could emerge to specifically target CTC clusters. Blocking their formation, disrupting their cohesion, or preventing their ability to survive in the bloodstream could offer new ways to prevent metastasis in aggressive cancers. Continued studies will be essential to further elucidate the biological pathways involved in CTC cluster-mediated metastasis and develop potential treatment interventions.2425

References

  1. Ring A, Nguyen-Sträuli BD, Wicki A, Aceto N (February 2023). "Biology, vulnerabilities and clinical applications of circulating tumour cells". Nature Reviews. Cancer. 23 (2): 95–111. doi:10.1038/s41568-022-00536-4. PMC 9734934. PMID 36494603. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9734934 ↩

  2. Allen TA, Asad D, Amu E, Hensley MT, Cores J, Vandergriff A, et al. (September 2019). "Circulating tumor cells exit circulation while maintaining multicellularity, augmenting metastatic potential". Journal of Cell Science. 132 (17). doi:10.1242/jcs.231563. PMC 6771143. PMID 31409692. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771143 ↩

  3. Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, et al. (August 2014). "Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis". Cell. 158 (5): 1110–1122. doi:10.1016/j.cell.2014.07.013. PMC 4149753. PMID 25171411. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149753 ↩

  4. Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, et al. (August 2014). "Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis". Cell. 158 (5): 1110–1122. doi:10.1016/j.cell.2014.07.013. PMC 4149753. PMID 25171411. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149753 ↩

  5. Allen TA, Asad D, Amu E, Hensley MT, Cores J, Vandergriff A, et al. (September 2019). "Circulating tumor cells exit circulation while maintaining multicellularity, augmenting metastatic potential". Journal of Cell Science. 132 (17). doi:10.1242/jcs.231563. PMC 6771143. PMID 31409692. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771143 ↩

  6. Au SH, Storey BD, Moore JC, Tang Q, Chen YL, Javaid S, et al. (May 2016). "Clusters of circulating tumor cells traverse capillary-sized vessels". Proceedings of the National Academy of Sciences of the United States of America. 113 (18): 4947–4952. Bibcode:2016PNAS..113.4947A. doi:10.1073/pnas.1524448113. PMC 4983862. PMID 27091969. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4983862 ↩

  7. Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, et al. (August 2014). "Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis". Cell. 158 (5): 1110–1122. doi:10.1016/j.cell.2014.07.013. PMC 4149753. PMID 25171411. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149753 ↩

  8. Sayed ZS, Khattap MG, Madkour MA, Yasen NS, Elbary HA, Elsayed RA, et al. (April 2024). "Circulating tumor cells clusters and their role in Breast cancer metastasis; a review of literature". Discover Oncology. 15 (1): 94. doi:10.1007/s12672-024-00949-7. PMC 10984915. PMID 38557916. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10984915 ↩

  9. Schuster E, Taftaf R, Reduzzi C, Albert MK, Romero-Calvo I, Liu H (November 2021). "Better together: circulating tumor cell clustering in metastatic cancer". Trends in Cancer. 7 (11): 1020–1032. doi:10.1016/j.trecan.2021.07.001. PMC 8541931. PMID 34481763. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541931 ↩

  10. Aceto N, Toner M, Maheswaran S, Haber DA (September 2015). "En Route to Metastasis: Circulating Tumor Cell Clusters and Epithelial-to-Mesenchymal Transition". Trends in Cancer. 1 (1): 44–52. doi:10.1016/j.trecan.2015.07.006. PMID 28741562. /wiki/Doi_(identifier) ↩

  11. Sarioglu AF, Aceto N, Kojic N, Donaldson MC, Zeinali M, Hamza B, et al. (July 2015). "A microfluidic device for label-free, physical capture of circulating tumor cell clusters". Nature Methods. 12 (7): 685–691. doi:10.1038/nmeth.3404. PMC 4490017. PMID 25984697. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490017 ↩

  12. Allen TA, Cullen MM, Hawkey N, Mochizuki H, Nguyen L, Schechter E, et al. (2021). "A Zebrafish Model of Metastatic Colonization Pinpoints Cellular Mechanisms of Circulating Tumor Cell Extravasation". Frontiers in Oncology. 11: 641187. doi:10.3389/fonc.2021.641187. PMC 8495265. PMID 34631514. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495265 ↩

  13. Sarioglu AF, Aceto N, Kojic N, Donaldson MC, Zeinali M, Hamza B, et al. (July 2015). "A microfluidic device for label-free, physical capture of circulating tumor cell clusters". Nature Methods. 12 (7): 685–691. doi:10.1038/nmeth.3404. PMC 4490017. PMID 25984697. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490017 ↩

  14. Amintas S, Bedel A, Moreau-Gaudry F, Boutin J, Buscail L, Merlio JP, et al. (April 2020). "Circulating Tumor Cell Clusters: United We Stand Divided We Fall". International Journal of Molecular Sciences. 21 (7): 2653. doi:10.3390/ijms21072653. PMC 7177734. PMID 32290245. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177734 ↩

  15. Allen TA, Asad D, Amu E, Hensley MT, Cores J, Vandergriff A, et al. (September 2019). "Circulating tumor cells exit circulation while maintaining multicellularity, augmenting metastatic potential". Journal of Cell Science. 132 (17). doi:10.1242/jcs.231563. PMC 6771143. PMID 31409692. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771143 ↩

  16. Lawrence R, Watters M, Davies CR, Pantel K, Lu YJ (July 2023). "Circulating tumour cells for early detection of clinically relevant cancer". Nature Reviews. Clinical Oncology. 20 (7): 487–500. doi:10.1038/s41571-023-00781-y. PMC 10237083. PMID 37268719. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10237083 ↩

  17. Cheung KJ, Padmanaban V, Silvestri V, Schipper K, Cohen JD, Fairchild AN, et al. (February 2016). "Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters". Proceedings of the National Academy of Sciences of the United States of America. 113 (7): E854 – E863. Bibcode:2016PNAS..113E.854C. doi:10.1073/pnas.1508541113. PMC 4763783. PMID 26831077. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763783 ↩

  18. Au SH, Storey BD, Moore JC, Tang Q, Chen YL, Javaid S, et al. (May 2016). "Clusters of circulating tumor cells traverse capillary-sized vessels". Proceedings of the National Academy of Sciences of the United States of America. 113 (18): 4947–4952. Bibcode:2016PNAS..113.4947A. doi:10.1073/pnas.1524448113. PMC 4983862. PMID 27091969. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4983862 ↩

  19. Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, et al. (August 2014). "Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis". Cell. 158 (5): 1110–1122. doi:10.1016/j.cell.2014.07.013. PMC 4149753. PMID 25171411. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149753 ↩

  20. Allen TA, Gracieux D, Talib M, Tokarz DA, Hensley MT, Cores J, et al. (January 2017). "Angiopellosis as an Alternative Mechanism of Cell Extravasation". Stem Cells. 35 (1): 170–180. doi:10.1002/stem.2451. PMC 5376103. PMID 27350343. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376103 ↩

  21. Allen TA, Asad D, Amu E, Hensley MT, Cores J, Vandergriff A, et al. (September 2019). "Circulating tumor cells exit circulation while maintaining multicellularity, augmenting metastatic potential". Journal of Cell Science. 132 (17). doi:10.1242/jcs.231563. PMC 6771143. PMID 31409692. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771143 ↩

  22. Sayed ZS, Khattap MG, Madkour MA, Yasen NS, Elbary HA, Elsayed RA, et al. (April 2024). "Circulating tumor cells clusters and their role in Breast cancer metastasis; a review of literature". Discover Oncology. 15 (1): 94. doi:10.1007/s12672-024-00949-7. PMC 10984915. PMID 38557916. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10984915 ↩

  23. Taftaf R, Liu X, Singh S, Jia Y, Dashzeveg NK, Hoffmann AD, et al. (August 2021). "ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer". Nature Communications. 12 (1): 4867. Bibcode:2021NatCo..12.4867T. doi:10.1038/s41467-021-25189-z. PMC 8358026. PMID 34381029. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358026 ↩

  24. Allen TA (March 2024). "The Role of Circulating Tumor Cells as a Liquid Biopsy for Cancer: Advances, Biology, Technical Challenges, and Clinical Relevance". Cancers. 16 (7): 1377. doi:10.3390/cancers16071377. PMC 11010957. PMID 38611055. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11010957 ↩

  25. Khoo BL, Grenci G, Lim YB, Lee SC, Han J, Lim CT (January 2018). "Expansion of patient-derived circulating tumor cells from liquid biopsies using a CTC microfluidic culture device". Nature Protocols. 13 (1): 34–58. doi:10.1038/nprot.2017.125. PMID 29215634. /wiki/Doi_(identifier) ↩