1. ALK+ Anaplastic Large Cell Lymphoma (ALCL)-Derived Exosomes Carry ALK Signaling Proteins and Interact with Tumor Microenvironment
- Author
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Panaretakis, Dimitrios Chioureas, Janina Beck, George Baltatzis, Ioulia Vardaki, Pedro Fonseca, Nikolaos Tsesmetzis, Francisco Vega, Vasiliki Leventaki, Aristides G. Eliopoulos, Elias Drakos, George Z. Rassidakis, and Theocharis
- Subjects
hemic and lymphatic diseases ,lymphoma ,exosomes ,microenvironment ,NPM-ALK ,cytokines - Abstract
The oncogenic pathways activated by the NPM-ALK chimeric kinase of ALK+ anaplastic large cell lymphoma (ALCL) are well characterized; however, the potential interactions of ALK signaling with the microenvironment are not yet known. Here we report that ALK+ ALCL-derived exosomes contain critical components of ALK signaling as well as CD30, and that exosome uptake by lymphoid cells led to increased proliferation and expression of critical antiapoptotic proteins by the recipient cells. The bone marrow fibroblasts highly uptake ALK+ ALCL-derived exosomes and acquire a cancer-associated fibroblast (CAF) phenotype. Moreover, exosome-mediated activation of stromal cells altered the cytokine profile of the microenvironment. These interactions may contribute to tumor aggressiveness and possibly resistance to treatment.
- Published
- 2022
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