Am80 inhibits stromal cell-derived factor-1-induced chemotaxis in T-cell acute lymphoblastic leukemia cells

Abstract

C-X-C motif chemokine receptor 4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) play a potent role in metastasis and infiltration of many types of tumors, including T-cell acute lymphoblastic leukemia (T-ALL), into the central nervous system or lymph nodes. Although higher levels of CXCR4 expression have been shown to correlate with shorter survival of patients, effective drugs affecting cell surface CXCR4 expression are still unknown. In the present study, we examined the effects of a synthetic retinoid Am80 on CXCR4 expression of cultured T-ALL cells, such as Jurkat. Am80 inhibited surface CXCR4 expression and SDF-1-induced chemotaxis by the acceleration of CXCR4 internalization via activation of conventional PKC. Am80 may be an effective drug to inhibit the extramedullary infiltration of T-ALL cells.

Keywords:

• Am80
• CXCR4
• protein kinase C
• T-cell acute lymphoblastic leukemia

Acknowledgements

We are indebted to Miss Emiko Ushijima and Miss Yuka Yoshimura for providing excellent technical assistance throughout this investigation. This study was supported in part by a scientific grant from TMRC Inc., Tokyo, Japan.