Basal autophagy is pivotal for Hodgkin and Reed-Sternberg cells’ survival and growth revealing a new strategy for Hodgkin lymphoma treatment
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Katrin Birkenmeier1, Katharina Moll1, Sebastian Newrzela1, Sylvia Hartmann1, Stefan Dröse2, Martin-Leo Hansmann1
1Dr. Senckenberg Institute of Pathology, University Hospital of Frankfurt, 60596 Frankfurt am Main, Germany
2Clinic of Anesthesiology, Intensive-Care Medicine and Pain Therapy, Goethe-University Hospital, 60596 Frankfurt am Main, Germany
Katrin Birkenmeier, email: [email protected]
Keywords: B-cell lymphoma, Hodgkin lymphoma, autophagy, lymphoma pathogenesis, targeted therapy
Received: February 1, 2016 Accepted: May 19, 2016 Published: June 27, 2016
As current classical Hodgkin lymphoma (cHL) treatment strategies have pronounced side-effects, specific inhibition of signaling pathways may offer novel strategies in cHL therapy. Basal autophagy, a regulated catabolic pathway to degrade cell’s own components, is in cancer linked with both, tumor suppression or promotion. The finding that basal autophagy enhances tumor cell survival would thus lead to immediately testable strategies for novel therapies. Thus, we studied its contribution in cHL.
We found constitutive activation of autophagy in cHL cell lines and primary tissue. The expression of key autophagy-relevant proteins (e.g. Beclin-1, ULK1) and LC3 processing was increased in cHL cells, even in lymphoma cases. Consistently, cHL cells exhibited elevated numbers of autophagic vacuoles and intact autophagic flux. Autophagy inhibition with chloroquine or inactivation of ATG5 induced apoptosis and reduced proliferation of cHL cells. Chloroquine-mediated inhibition of basal autophagy significantly impaired HL growth in-vivo in NOD SCID γc-/- (NSG) mice. We found that basal autophagy plays a pivotal role in sustaining mitochondrial function.
We conclude that cHL cells require basal autophagy for growth, survival and sustained metabolism making them sensitive to autophagy inhibition. This suggests basal autophagy as useful target for new strategies in cHL treatment.
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