Expression of the novel intermediate filament-associated protein restin in Hodgkin's disease and anaplastic large-cell lymphoma

Abstract

In this study, the expression of the novel intermediate filament protein Restin in human tissues was analyzed. Restin expression was studied by immunohistochemistry using polyclonal and monoclonal antibodies. Restin was not detected in normal tissues, a range of B- and T-cell non-Hodgkin's lymphomas, and nonlymphoid tumors. However, Restin was present in Reed-Sternberg cells and variants thereof in Hodgkin's disease, with the exception of the lymphocyte-predominant, paragranuloma subtype. Restin was also highly expressed in anaplastic large-cell lymphoma (so-called Ki-1 lymphoma). As expected, Restin was also expressed in Hodgkin cell lines L428, L428KSA, Co, and KM-H2 and the anaplastic large-cell lymphoma cell line Karpas 299, which was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting, as well as Northern blotting. The presence of Restin in both Hodgkin's disease and anaplastic large-cell lymphoma is intriguing and might indicate a role of this structural protein in the pathogenesis of both conditions.

Expression of Functional Interleukin-3 Receptors on Hodgkin and Reed-Sternberg Cells

“…38 In addition, functional IL-3Rs have been detected on normal B-cell precursors in the bone marrow 39 and on tumor cells from B-cell malignancies reflecting early and late stages of B-cell lymphopoiesis such as B-lineage acute lymphoblastic leukemias, 40 -42 follicular lymphomas, 43,44 chronic lymphocytic leukemias, 45 and malignant plasma cells precursors. 46 H-RS cells, along with immunoglobulin gene rearrangements, 34 -36 display impressive functional and phenotypic overlaps with dendritic cells (DCs), including antigen-presenting capacity, 3,4,47 expression of specific co-stimulatory molecules, [3][4][5]17,47,48 cytoskeleton-associated proteins, 49,50 and cytokines/chemokines. [3][4][5]7,8,51,52 Interestingly, IL-3R␣s have been also found to be expressed on a specific subset of human DC precursors of T-cell derivation, originally described as plasmacytoid T cells or plasmacytoid monocytes.…”

Regulation of tumor angiogenesis by the microtubule-binding protein CLIP-170

“…Several previous studies have implicated CLIP-170 in the pathogenesis of cancer. For example, overexpression of a splicing variant of CLIP-170 has been observed in Hodgkin's disease and anaplastic large-cell lymphoma (Bilbe et al, 1992;Delabie et al, 1992). CLIP-170 has also been shown to regulate lamellipodium formation and invasion of breast cancer cells (Suzuki and Takahashi, 2008).…”

“…CLIP-170 is a founding member of the +TIPs family and participates in cell migration by mediating the cortical capture of microtubules (Gouveia and Akhmanova, 2010). CLIP-170 has also been implicated in the pathogenesis of cancer; however, the underlying molecular mechanisms remain obscure (Bilbe et al, 1992;Delabie et al, 1992;Suzuki and Takahashi, 2008;Sun et al, 2012). In this study, our data demonstrate that CLIP-170 stimulates tumor angiogenesis by mediating vascular endothelial cell polarization and migration, and establish a critical link between the pathological role of CLIP-170 and its role as a component of D 0 h 12 h 24 h 36 h 48 h 0 h 12 h 24 h 36 h 48 h 9 7 5 3 1 Normal tissue Tumor + Adjacent tissue MCF7 MDA-MB-231 we found that #1, but not #2, CLIP-170 siRNA signifi cantly decreased tumor vascularization ( Fig.…”

Exclusion of 5 functional candidate genes for distal hereditary motor neuropathy type II (distal HMN II) linked to 12q24.3

“…Cytoplasmic linker proteins (CLIPs) are a class of proteins believed to mediate the initial, static interaction of cytoplasmic organelles with microtubules Rickard & Kreis, 1996). RSN (CLIP170j35), like its 3 other isoforms (CLIP170, CLIP170j11, CLIP170j11j35), is an intermediate filamentassociated protein found to be highly expressed in Reed-Sternberg cells which are diagnostic for Hodgkin's disease (Delabie et al 1992). Other studies demonstrated RSN expression in a wide variety of human tissues .…”

“…PXN is a cytoskeletal protein found at sites where cells adhere to the extracellular matrix (ECM), and mediates bi-directional signalling between the actin cytoskeleton and the ECM by coupling to integrins (Burridge et al 1992 ;Salgia et al 1995). RSN is an intermediate filament-associated protein (Delabie et al 1992). RPLP0 is a component of the eukaryotic ribosome stalk (Moller & Maassen, 1986).…”