TY - JOUR
T1 - ALK+ Anaplastic Large Cell Lymphoma (ALCL)-Derived Exosomes Carry ALK Signaling Proteins and Interact with Tumor Microenvironment
AU - Chioureas, Dimitrios
AU - Beck, Janina
AU - Baltatzis, George
AU - Vardaki, Ioulia
AU - Fonseca, Pedro
AU - Tsesmetzis, Nikolaos
AU - Vega, Francisco
AU - Leventaki, Vasiliki
AU - Eliopoulos, Aristides G.
AU - Drakos, Elias
AU - Rassidakis, George Z.
AU - Panaretakis, Theocharis
N1 - Funding Information:
Funding: This project was supported by grants from Swedish Cancer Foundation and Radiumhem-mets Research Foundation to T.P. This project was also supported by research grants from Cancer-fonden (Swedish Cancer Society, 19 0277 PJ), Barncancerfonden (Swedish Childhood Cancer Fund, PR2021-0113), and Radiumhemmets Forskningsfonder (Radiumhemmets Research Foundation, King Gustaf V Jubilee Fund, project no. 204133) to G.Z.R.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - 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.
AB - 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.
KW - cytokines
KW - exosomes
KW - lymphoma
KW - microenvironment
KW - NPM-ALK
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U2 - 10.3390/cancers14122939
DO - 10.3390/cancers14122939
M3 - Article
C2 - 35740600
AN - SCOPUS:85131897547
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 12
M1 - 2939
ER -