Title:Arachidonic Acid Induces the Migration of MDA-MB-231 Cells by Activating Raft-associated Leukotriene B4 Receptors
Volume: 5
Author(s): Atasi De Chatterjee, Debarshi Roy, Priscilla Guevara, Rituraj Pal, Mahesh Narayan, Sukla Roychowdhury and Siddhartha Das*
Affiliation:
- The Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX 79968-0519,United States
Keywords:
Breast cancer, MDA-MB-231, MCF-7, eicosanoids, leukotrienes, lipid rafts.
Abstract: Background: The migration of tumor cells is critical in spreading cancers through the
lymphatic nodes and circulatory systems. Although arachidonic acid (AA) and its soluble metabolites
have been shown to induce the migration of breast and colon cancer cells, the mechanism by which it
induces such migration has not been fully understood.
Objective: The effect of AA on migratory responses of the MDA-MB-231 cell line (a triple-negative
breast cancer cell) was examined and compared with MCF-7 (estrogen-receptor positive) breast cancer
cells to elucidate the mechanism of AA-induced migration.
Methods: Migrations of breast cancer cells were examined with the help of wound-healing assays.
AA-induced eicosanoid synthesis was monitored by RP-HPLC. Cellular localizations of lipoxygenase
and lipid rafts were assessed by immunoblot and confocal microscopy.
Results: AA treatment stimulated the synthesis of leukotriene B4 (LTB4) and HETE-8, but lowered
the levels of prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), and HETE-5 in MDA-MB-231
cells. Further analysis indicated that AA increased the expression of 5-lipoxygenase (5-LOX) in this
cell line and inhibiting its expression by small molecule inhibitors lowered the production of LTB4
and reduced migration. In contrast, MCF-7 cells did not show any appreciable changes in eicosanoid
synthesis, 5-LOX expression, or cellular migration.
Conclusion: Our results suggest that AA treatment activates the BLT1 receptor (present in membrane
microdomains) and stimulates the synthesis of LTB4 production, which is likely to be associated with
the migration of MDA-MB-231 cells.
