Lysophosphatidic acid (LPA) is a
lipid mediator with diverse effects on various cells. Here, we investigated the effects of LPA on human colon
carcinoma DLD1 cells. Northern blot analysis revealed that DLD1 highly expressed LPA1/Edg-2 but showed only low expression of LPA2/Edg-4 and no expression of LPA3/Edg-7 at the
mRNA level. Western blot analysis revealed that DLD1 cells highly expressed LPA1 at the
protein level. Using the Boyden chamber assay, LPA markedly increased DLD1 cell migration at concentrations as low as 10 nM, with maximum stimulation at 100 nM (3.6-fold increase). Checkerboard analysis indicated that LPA stimulated both the chemotactic and chemokinetic migration of DLD1 cells. LPA induced a dose-dependent increase in the proliferation of DLD1 cells (3.2-fold increase at 20 microM). Furthermore, LPA stimulated DLD1 cell adhesion to
collagen type I (2.0-fold increase
at 10 microM) and also stimulated the secretion of both
vascular endothelial growth factor (1.4-fold increase at 20 microM) and
interleukin 8 (19-fold increase at 20 microM) by ELISA. In contrast, as for
matrix metalloproteinase, LPA had no significant effect on pro-
matrix metalloproteinase-2 secretion and its activation, as measured by Western blot analysis. Thus, LPA, at concentrations that are present physiologically, enhanced DLD1 cell migration, proliferation, adhesion, and secretion of angiogenic factors, all of which are crucial for
cancer metastasis. In comparison, other human colon
carcinoma cells (HT29 and WiDR) exclusively expressed LPA2. LPA enhanced their proliferation and secretion of angiogenic factors, whereas LPA did not enhance migration or adhesion. Our results suggest that LPA acts as a potent stimulator of
colon cancer progression, although the binding to LPA1 and LPA2 induces slightly different responses.