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Understanding Systemic Signaling and Inter-Organ Communication between Tumor Cells and the Immune System in Drosophila Model of Cancer Cachexia
CC BY 4.0 · Indian J Med Paediatr Oncol 2024; 45(S 01): S1-S16
DOI: DOI: 10.1055/s-0044-1788243
*Corresponding author: (email: rkhadilkar@actrec.gov.in).
Abstract
Background: Cancer Cachexia is a multifactorial syndrome that involves systemic metabolic deregulation in several organs. Muscle wasting and systemic inflammation are the hallmark features of cachexia. Tumors produce signaling molecules that drive systemic wasting. However, how this crosstalk is governed and whether there are mediators that directly regulate cachexia is unknown.
Materials and Methods: We have induced epithelial tumors in Drosophila larval imaginal discs and gut using various mutant transgenes employing the UAS-GAL4 technology and validated the cachexia phenotypes like muscle wasting and lipolysis. We have also assessed the effects of the epithelial tumors on immune homeostasis in the flies.
Results: Upon tumor induction, an increase in the number of mitotically active cells and a sizeable increase in the overall tissue volume is seen. Increased lipolysis in the fat body and muscle wasting is seen in the larval cuticular muscle, thus validating cancer cachexia. We further probe the crosstalk between the epithelial tumor and the immune system in the flies. We find that tumor induced cachexia adversely affects the innate immune response even in the larval cachectic models. We are currently characterizing this inter-organ communication and its impact on stem cell and organ homeostasis.
Conclusion: Tumor-induced cachexia causes systemic effects by disrupting immune homeostasis. This study will shed light on understanding the mechanistic underpinnings of what are the key mediators of cachexia and how tumor–distant organ communication can specifically impact the innate immune response in the flies.
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
*Corresponding author: (email: rkhadilkar@actrec.gov.in).
Abstract
Background: Cancer Cachexia is a multifactorial syndrome that involves systemic metabolic deregulation in several organs. Muscle wasting and systemic inflammation are the hallmark features of cachexia. Tumors produce signaling molecules that drive systemic wasting. However, how this crosstalk is governed and whether there are mediators that directly regulate cachexia is unknown.
Materials and Methods: We have induced epithelial tumors in Drosophila larval imaginal discs and gut using various mutant transgenes employing the UAS-GAL4 technology and validated the cachexia phenotypes like muscle wasting and lipolysis. We have also assessed the effects of the epithelial tumors on immune homeostasis in the flies.
Results: Upon tumor induction, an increase in the number of mitotically active cells and a sizeable increase in the overall tissue volume is seen. Increased lipolysis in the fat body and muscle wasting is seen in the larval cuticular muscle, thus validating cancer cachexia. We further probe the crosstalk between the epithelial tumor and the immune system in the flies. We find that tumor induced cachexia adversely affects the innate immune response even in the larval cachectic models. We are currently characterizing this inter-organ communication and its impact on stem cell and organ homeostasis.
Conclusion: Tumor-induced cachexia causes systemic effects by disrupting immune homeostasis. This study will shed light on understanding the mechanistic underpinnings of what are the key mediators of cachexia and how tumor–distant organ communication can specifically impact the innate immune response in the flies.
No conflict of interest has been declared by the author(s).
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India