Protrusion-guided extracellular vesicles mediate CD30 trans-signalling in the microenvironment of Hodgkin's lymphoma.

[hodgkin lymphoma, classical]

Classical Hodgkin 's lymphoma (cHL )-affected lymphoid tissue contains only a few malignant Hodgkin and Reed -Sternberg (HRS ) cells , which are disseminated within a massive infiltrate of reactive cells . In particular , the innate immune infiltrate is deemed to support tumour growth by direct cell-cell interaction . Since they are rarely found in close proximity to the malignant cells in situ , we investigated whether cHL-derived extracellular vesicles might substitute for a direct cell-cell contact . We studied the crosstalk of the transmembrane proteins CD 30 and CD 30 ligand (CD 30 L ) because they are selectively expressed on HRS and innate immune cells , respectively . Here , we showed that HRS cells released both the ectodomain as a soluble molecule (sCD 30 ) and the entire receptor on the surface of extracellular vesicles . The vesicle diameter was 40 -800 nm , as determined by cryo- and immune electron microscopy . In addition to CD 30 , typical extracellular vesicle markers were detected by mass spectrometry and flow cytometry , including tetraspanins , flotillins , heat shock proteins and adhesion molecules . In contrast to sCD 30 , vesicles caused a CD 30 -dependent release of interleukin-8 in CD 30 L (+) eosinophil-like EoL-1 cells and primary granulocytes from healthy donors , underscoring the functionality of CD 30 on vesicles . In extracellular matrix (ECM )-embedded culture of HRS cells , a network of actin and tubulin-based protrusions guided CD 30 (+) vesicles into the micro-environment . This network targeted CD 30 (+) vesicles towards distant immune cells and caused a robust polarization of CD 30 L . Confocal laser scanning microscopy of 30 Âµm sections showed a CD 30 vesicle-containing network also in cHL-affected lymphoid tissue of both mixed -cellularity and nodular sclerosing subtypes . This network might facilitate the communication between distant cell types in cHL tissue and allow a functional CD 30 -CD 30 L interaction in trans . The tubulin backbone of the network may provide a target for the therapy of cHL with antitubulin-based CD 30 antibody constructs .

Diseases
Validation

Diseases presenting "respectively" symptom

adrenal incidentaloma

allergic bronchopulmonary aspergillosis

alpha-thalassemia

benign recurrent intrahepatic cholestasis

carcinoma of the gallbladder

congenital adrenal hyperplasia

congenital diaphragmatic hernia

congenital toxoplasmosis

cushing syndrome

cystinuria

dedifferentiated liposarcoma

dentin dysplasia

dentinogenesis imperfecta

epidermolysis bullosa simplex

esophageal squamous cell carcinoma

familial hypocalciuric hypercalcemia

harlequin ichthyosis

hereditary cerebral hemorrhage with amyloidosis

hirschsprung disease

hodgkin lymphoma, classical

holt-oram syndrome

kallmann syndrome

lamellar ichthyosis

liposarcoma

neonatal adrenoleukodystrophy

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

oral submucous fibrosis

pendred syndrome

pleomorphic liposarcoma

primary effusion lymphoma

proteus syndrome

pyruvate dehydrogenase deficiency

scrub typhus

triple a syndrome

von hippel-lindau disease

well-differentiated liposarcoma

wolf-hirschhorn syndrome

You can validate or delete this automatically detected symptom