Mesenchymal stromal cells orchestrate follicular lymphoma cell niche through the CCL2-dependent recruitment and polarization of monocytes.

Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE

Publication: 2021- : [New York] : Elsevier
Original Publication: New York, Grune & Stratton [etc.]

B-Lymphocytes/*metabolism ; Cell Polarity/*physiology ; Chemokine CCL2/*metabolism ; Lymphoma, Follicular/*pathology ; Mesenchymal Stem Cells/*cytology ; Monocytes/*cytology ; Stromal Cells/*cytology; Adult ; Aged ; B-Lymphocytes/cytology ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Blotting, Western ; Cell Differentiation ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Chemokine CCL2/genetics ; Female ; Gene Expression Profiling ; Humans ; Lymphoma, Follicular/etiology ; Lymphoma, Follicular/metabolism ; Male ; Mesenchymal Stem Cells/metabolism ; Middle Aged ; Monocytes/metabolism ; Oligonucleotide Array Sequence Analysis ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Stromal Cells/metabolism

Accumulating evidence indicates that infiltrating stromal cells contribute directly and indirectly to tumor growth in a wide range of cancers. In follicular lymphoma (FL), malignant B cells are found admixed with heterogeneous lymphoid-like stromal cells within invaded lymph nodes and BM. In addition, mesenchymal stromal cells (MSCs) support in vitro FL B-cell survival, in particular after their engagement toward lymphoid differentiation. We show here that BM-MSCs obtained from patients with FL (FL-MSCs) display a specific gene expression profile compared with MSCs obtained from healthy age-matched donors (HD-MSCs). This FL-MSC signature is significantly enriched for genes associated with a lymphoid-like commitment. Interestingly, CCL2 could be detected at a high level within the FL-cell niche, is up-regulated in HD-MSCs by coculture with malignant B cells, and is overexpressed by FL-MSCs, in agreement with their capacity to recruit monocytes more efficiently than HD-MSCs. Moreover, FL-MSCs and macrophages cooperate to sustain malignant B-cell growth, whereas FL-MSCs drive monocyte differentiation toward a proangiogenic and lipopolysaccharide-unresponsive phenotype close to that of tumor-associated macrophages. Altogether, these results highlight the complex role of FL stromal cells that promote direct tumor B-cell growth and orchestrate FL-cell niche, thus emerging as a potential therapeutic target in this disease.

0 (Biomarkers, Tumor)
0 (CCL2 protein, human)
0 (Chemokine CCL2)
0 (RNA, Messenger)

Date Created: 20120201 Date Completed: 20120521 Latest Revision: 20210202

20221213

10.1182/blood-2011-08-370908

22289889