[Relationship between Chemotactic Factor CCL5 and Diabet-associated Diffuse Large B Cell Lymphoma].

Objective: To explore whether the chemotactic factor CCL5 is the major factor of diffuse large B cell lymphoma (DLBCL) induced by diabetes or not.

Methods: The normal human B cells and DLBCL cells were cultured in vitro; the RT-PCR was used to detect their CCL5 mRNA expression, the human DLBCL cell line and mouse-derived DLBCL cell line A20 were cultured in vitro by using glucose at 5 and 30 mmol/L, respectively, then their CCL5 mRNA expression was detected by PT-PCR; the diabetic mouse model was constructed through peritoneal injection of streptozotocin at low dose in the BALB/c mice; the cell lines with stably high and low expression of CCL5 were established via lentiviral transfection and the cell lines with low and high expression of CCL5 were subcutaneously injected into diabetic mice and mice with normal blood sugar level. According to blood sugar level, the experimental mice were divided into 2 groups: diabetic group (A group) and normal blood sugar group as control (B group); then according to CCL5 expression level, the A group and B group were divided as well into high expression group (A1 group and B1 group) and low expression group (A2 group and B2 group), respectively, the tumor-formation rate, tumor-formation time, tumor size and texture were analyzed, respectively; the CCL5 expression was detected by using HE staining of tumor tissue and immunohistochemical method.

Results: The expression of CCL5 mRNA in human DLBCL cell line cultured in vitro was higher than that in normal B cells (P < 0.05); the expressions of CCL5 mRNA in human DLBCL cells cultured in high sugar concentration in vitro and mouse DLBCL cells were higher than those in cells cultured in low sugar concentration (P < 0.05). The tumor-formation rates in diabetic mice injected with high and low expression of CCL5 cell line A20 were 93.3% in A1 group and 60% in A2 group; the their tumor-formation time was 7.0 ± 0.85 days in A1 group and 9.5 ± 2.8 days in A2 group, while the tumor formation rates in mice with normal blood sugar level were 20% in B1 group and 20% in B2 group, and their tumor-formation time was 12 ± 1.3 days and 14 ± 2.5 days respectively; the CCL5 expression level in tumor tissue of diabetic mice was higher than that in tumor tissue of mice with normal blood sugar level.

Conclusion: The high blood glucose level can casase increase of DLBCL risk and promote the tumor growth; the chemotactic factor CCL5 may play an important role in the growth and migration of DLBCL caused by diabetes mellitus.