Identification of stromal proteins overexpressed in nodular sclerosis Hodgkin lymphoma

Abstract

Hodgkin lymphoma (HL) represents a category of lymphoid neoplasms with unique features, notably the usual scarcity of tumour cells in involved tissues. The most common subtype of classical HL, nodular sclerosis HL, characteristically comprises abundant fibrous tissue stroma. Little information is available about the protein composition of the stromal environment from HL. Moreover, the identification of valid protein targets, specifically and abundantly expressed in HL, would be of utmost importance for targeted therapies and imaging, yet the biomarkers must necessarily be accessible from the bloodstream. To characterize HL stroma and to identify potentially accessible proteins, we used a chemical proteomic approach, consisting in the labelling of accessible proteins and their subsequent purification and identification by mass spectrometry. We performed an analysis of potentially accessible proteins in lymph node biopsies from HL and reactive lymphoid tissues, and in total, more than 1400 proteins were identified in 7 samples. We have identified several extracellular matrix proteins overexpressed in HL, such as versican, fibulin-1, periostin, and other proteins such as S100-A8. These proteins were validated by immunohistochemistry on a larger series of biopsy samples, and bear the potential to become targets for antibody-based anti-cancer therapies.

Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma

“…Other ECM-associated proteins were more abundant in non-relapsing HL (e.g., fibulin-1, EGF-containing fibulin-like extracellular matrix protein 1). Fibulin-1, which is expressed mainly by cancer cells and only by some fibroblasts [36], has been reported to be overexpressed in lymph node biopsies from HL patients [37].…”

Proteomic approaches to the study of malignant lymphoma: Analyses on patient samples

“…It could be interesting to investigate this actin‐binding protein and its function in regard to HL/NHL in future studies. Another approach to identify HL diagnostic markers was performed by Kischel et al., who identified several biotinylated proteins with differential expression comparing HL and reactive LN specimens . The use of biotinylated proteins as biomarkers permits the identification of accessible antigens, in particular ECM proteins.…”

“…The use of biotinylated proteins as biomarkers permits the identification of accessible antigens, in particular ECM proteins. Following biotinylation and subsequent identification by LC‐MS/MS, several ECM proteins were identified as being differentially expressed . These proteins were preferentially localized at the cell membrane or in the extracellular compartment .…”

“…Following biotinylation and subsequent identification by LC‐MS/MS, several ECM proteins were identified as being differentially expressed . These proteins were preferentially localized at the cell membrane or in the extracellular compartment . Among proteins overexpressed in HL compared to reactive LN, three proteins were further assessed by IHC and the elevated protein expressions were confirmed in most cases, that is, for versican (13/17), fibulin‐1 (12/17), and periostin (17/17) .…”

FBLN1 (fibulin 1)

“…Disease Using a chemical proteomic approach in Hodgkin Lymphoma (HL), Kischel and coauthors identified several extracellular matrix proteins, including fibulin-1, overexpressed in HL (Kischel et al, 2011). Based on its high expression levels in HL biopsy samples fibulin-1 has been suggested as a potential targets for HL immunotherapy.…”