Microenvironmental interactions between endothelial and lymphoma cells: a role for the canonical WNT pathway in Hodgkin lymphoma

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LINKE F. HARENBERG M. NIETERT M.M. ZAUNIG S. F. von Bonin ARLT A. SZCZEPANOWSKI M. WEICH HA LUTZ S. DULLIN C. JANOVSKÁ Pavlína KRAFČÍKOVÁ Michaela TRANTÍREK Lukáš OVESNÁ Petra KLAPPER W. BEISSBARTH T. ALVES F. BRYJA Vítězslav TRÜMPER L. WILTING J. KUBE Dieter

Druh Článek v odborném periodiku
Časopis / Zdroj Leukemia
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
WWW https://www.nature.com/articles/leu2016232
Doi http://dx.doi.org/10.1038/leu.2016.232
Obor Genetika a molekulární biologie
Klíčová slova CHRONIC LYMPHOCYTIC-LEUKEMIA; CHEMOKINE RECEPTOR CCR7; FUNCTIONAL CD30 LIGAND; GROWTH-FACTOR; CONSTITUTIVE ACTIVATION; TUMOR; EXPRESSION; DISEASE; DISSEMINATION; VEGF
Popis The interaction between vascular endothelial cells (ECs) and cancer cells is of vital importance to understand tumor dissemination. A paradigmatic cancer to study cell-cell interactions is classical Hodgkin Lymphoma (cHL) owing to its complex microenvironment. The role of the interplay between cHL and ECs remains poorly understood. Here we identify canonical WNT pathway activity as important for the mutual interactions between cHL cells and ECs. We demonstrate that local canonical WNT signaling activates cHL cell chemotaxis toward ECs, adhesion to EC layers and cell invasion using not only the Wnt-inhibitor Dickkopf, tankyrases and casein kinase 1 inhibitors but also knockdown of the lymphocyte enhancer binding-factor 1 (LEF-1) and beta-catenin in cHL cells. Furthermore, LEF-1- and beta-catenin-regulated cHL secretome promoted EC migration, sprouting and vascular tube formation involving vascular endothelial growth factor A (VEGF-A). Importantly, high VEGFA expression is associated with a worse overall survival of cHL patients. These findings strongly support the concept that WNTs might function as a regulator of lymphoma dissemination by affecting cHL cell chemotaxis and promoting EC behavior and thus angiogenesis through paracrine interactions.
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