[The role of stromal cell derived factor-1/CXCR4 biological axis in tumor metastasis of non-Hodgkin lymphoma]

Abstract

Objective: To study the expression of stromal cell derived factor-1 (SDF-1) and its receptor CXCR4 in non-Hodgkin lymphoma (NHL), and to investigate the role of this biological axis in tumor metastasis of NHL.

Methods: Specimens of bone marrow were collected from 4 patients with NHL with bone marrow infiltration and 4 cases of NHL without bone marrow infiltration, and 4 patients with benign hepatopathy with normal myelogram. Lymphoma specimens were collected from 7 cases of NHL and 3 cases of reactive proliferative lymphadenitis. The level of SDF-1alpha mRNA in the stromal cells of bone marrow and lymph node were determined by RT-PCR. The CXCR4 expression on lymphoma cells freshly isolated from bone marrow and lymph node of the NHL patients were studied by flow cytometry. Transwell assay was performed, the upper chamber being added with suspension of cells newly isolated from lymph nodes or bone marrow undergoing co-incubation with ant-CXCR4 monoclonal antibody or not, and the lower chamber added with culture fluid with or without recombinant human SDF-1alpha (rhSDF-1alpha). The migration rate of the primary lymphoma cells towards rhSDF-1alpha was calculated.

Results: The expression levels of CXCR4 on the lymphoma cells isolated from the bone marrow involved or not involved by NHL were both significantly higher than that of the mononuclear cells from normal bone marrow (both P < 0.01), whereas the CXCR4 expression level on the lymphoma cells from the lymph nodes of the NHL patients was also significantly higher than that of the mononuclear cells from the lymph nodes of reactive proliferative lymphadenitis (P < 0.01). The SDF-1alpha mRNA expression level in the stromal cells isolated from the bone marrow involved by NHL was significantly higher than those of the stromal cells of bone marrow not involved by NHL and the normal bone marrow (both P < 0.01). Moreover, the SDF-1alpha expression level in the lymph node stromal cells of all the NHL patients was also significantly higher than that of the patients with reactive proliferative lymphadenitis (P < 0.01). Transwell assay revealed that all three kinds of primary lymphoma cells migrated towards rhSDF-1alpha effectively, and this migration was markedly inhibited by the addition of anti-CXCR4 monoclonal antibody to the lymphoma cells (all P < 0.01).

Conclusion: SDF-1/CXCR4 axis plays a uniquely important biological role in mediating tumor metastasis of NHL.