Stromalniche communalities underscore the contribution of the matricellular proteinSPARC to B-cell development and lymphoid malignancies

Alessandro Gulino, Carla Guarnotta, Claudio Tripodo, Paola Portararo, Ilaria Torselli, Caterina Vitali, Matteo Dugo, Laura Botti, Patrizia Casalini, Patrizia Casalini, Sabina Sangaletti, Barbara Cappetti, Claudia Chiodoni, Patrizia Casalini, Mario P. Colombo

Risultato della ricerca: Articlepeer review

21 Citazioni (Scopus)

Abstract

Neoplastic B-cell clones commonly arise within secondary lymphoid organs (SLO). However, during disease progression, lymphomatous cells may also colonize the bone marrow (BM), where they localize within specialized stromal niches, namely the osteoblastic and the vascular niche, according to their germinal center-or extra-follicular-derivation, respectively. We hypothesized the existence of common stromal motifs in BM and SLO B-cell lymphoid niches involved in licensing normal B-cell development as well as in fostering transformed B lymphoid cells. Thus, we tested the expression of prototypical mesenchymal stromal cell (MSC) markers and regulatory matricellular proteins in human BM and SLO under physiologically unperturbed conditions and during B-cell lymphoma occurrence. We identified common stromal features in the BM osteoblastic niche and SLO germinal center (GC) microenvironments, traits that were also enriched within BM infiltrates of GC-associated B-cell lymphomas, suggesting that stromal programs involved in central and peripheral B-cell lymphopoiesis are also involved in malignant B-cell nurturing. Among factors co-expressed by stromal elements within these different specialized niches, we identified the pleiotropic matricellular protein secreted protein acidic and rich in cysteine (SPARC). The actual role of stromal SPARC in normal B-cell lymphopoiesis, investigated in Sparc(-/-) mice and BM chimeras retaining the Sparc(-/-) genotype in host stroma, demonstrated defective BM and splenic B-cell lymphopoiesis. Moreover, in the Trp53 knockout (KO) lymphoma model, p53(-/-)/Sparc(-/-) double-KO mice displayed impaired spontaneous splenic B-cell lymphomagenesis and reduced neoplastic clone BM infiltration in comparison with their p53(-/-)/Sparc(+/+) counterparts. Our results are among the first to demonstrate the existence of common stromal programs regulating both the BM osteoblastic niche and the SLO GC lymphopoietic functions potentially fostering the genesis and progression of B-cell malignancies.
Lingua originaleEnglish
pagine (da-a)00-00
Numero di pagine0
RivistaOncoImmunology
Volume3
Stato di pubblicazionePublished - 2014

All Science Journal Classification (ASJC) codes

  • ???subjectarea.asjc.2700.2723???
  • ???subjectarea.asjc.2400.2403???
  • ???subjectarea.asjc.2700.2730???

Fingerprint

Entra nei temi di ricerca di 'Stromalniche communalities underscore the contribution of the matricellular proteinSPARC to B-cell development and lymphoid malignancies'. Insieme formano una fingerprint unica.

Cita questo