Migration Properties Distinguish Tumor Cells of Classical Hodgkin Lymphoma from Anaplastic Large Cell Lymphoma Cells.

Olga Goncharova,Nadine Flinner,Martin-Leo Hansmann,Claudia Döring,Sylvia Hartmann,Sandy Rikirsch,Julia Bein,Ralf Küppers,Marco Herling,Emmanuel Donnadieu

doi:10.3390/cancers11101484

Abstract

Anaplastic large cell lymphoma (ALCL) and classical Hodgkin lymphoma (cHL) are lymphomas that contain CD30-expressing tumor cells and have numerous pathological similarities. Whereas ALCL is usually diagnosed at an advanced stage, cHL more frequently presents with localized disease. The aim of the present study was to elucidate the mechanisms underlying the different clinical presentation of ALCL and cHL. Chemokine and chemokine receptor expression were similar in primary ALCL and cHL cases apart from the known overexpression of the chemokines CCL17 and CCL22 in the Hodgkin and Reed-Sternberg (HRS) cells of cHL. Consistent with the overexpression of these chemokines, primary cHL cases encountered a significantly denser T cell microenvironment than ALCL. Additionally to differences in the interaction with their microenvironment, cHL cell lines presented a lower and less efficient intrinsic cell motility than ALCL cell lines, as assessed by time-lapse microscopy in a collagen gel and transwell migration assays. We thus propose that the combination of impaired basal cell motility and differences in the interaction with the microenvironment hamper the dissemination of HRS cells in cHL when compared with the tumor cells of ALCL.

Highlights

Anaplastic large cell lymphoma (ALCL) is a CD30-expressing malignant lymphoma of T-cell origin [1,2]
To investigate whether the dissemination of lymphoma cells is dependent on the expression of chemokine receptors, we examined the expression of the chemokine receptors CXCR3, CCR4, CCR5 and CCR1 in primary cases of ALCL and Classical Hodgkin lymphoma (cHL) by immunohistochemistry
Chemokine receptors were chosen based on the hypothesis that ALCL tumor cells would be more similar to reactive T cells in chemokine receptor expression than Hodgkin and Reed-Sternberg (HRS) cells of cHL

Summary

Introduction

Anaplastic large cell lymphoma (ALCL) is a CD30-expressing malignant lymphoma of T-cell origin [1,2]. The cytomorphological hallmark of ALCL is the presence of tumor cells with large kidney shaped nuclei and abundant cytoplasm [5,6]. T-cell origin of ALCL [7], the expression of most T-cell markers is lost in this lymphoma [8]. Classical Hodgkin lymphoma (cHL) is another CD30-expressing malignant lymphoma [9] that shares morphological and phenotypical features with ALCL and can impose a difficult differential diagnosis. In contrast with ALCL, the Hodgkin and Reed-Sternberg (HRS) cells of cHL are derived from pre-apoptotic germinal center B cells [10,11] The expression of most B-cell markers is generally lost in cHL [12]

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