Login to Access Video or Poster Abstract: MP48-04
Sources of Funding: none

Introduction

Lysophosphatidic acid (LPA) is one of several physiologically active lipid mediators that promote cell proliferation, cell migration, and cell invasion and are present in serum, ascites, and urine. LPA receptor is considered a potential therapeutic target for treatment of some malignant cancers. Here, we evaluated the expression of LPA receptors, and effect of its receptor expression on recurrence, progression and survival rate in bladder cancer. Furthermore, we examined the bladder cancer invasion mechanism that LPA were associated.

Methods

Expression of LPA receptors in bladder cancer specimens from bladder cancer patients (Ta or T1; 49 patients and T2-T4; 17 patients) was examined using real-time PCR and immunohistochemical staining. Matrigel invasion assay, proliferation assay, cell morphological observations were conducted and Rho kinase (ROCK) expression, myosin light chain (MLC) phosphorylation were measured to assess the effects of LPA on T24 cells, which derive from bladder cancer.

Results

LPA receptor 1 (LPA1) mRNA expression was significantly higher in muscle-invasive bladder cancer (MIBC) specimens than in non-muscle-invasive bladder cancer (NMIBC) specimens. Strong LPA1 expression was evident on cell membranes of MIBC specimens. Cancer-specific survival rate was predominantly lower in LPA1 positive group. T24 cell invasion was increased by LPA treatment, and invasiveness was decreased by LPA1-siRNA or LPA1 inhibitor. LPA treatment increased Rho kinase1 (ROCK1) expression and phosphorylation of MLC, and induced morphological changes including lamellipodia formation and cell rounding.

Conclusions

Our results indicated that LPA1 expression was increased in bladder cancer with highly invasive potential. Furthermore, LPA signaling via LPA1 activation promoted bladder cancer invasion. Analyzing LPA1 expression might be useful for planning of bladder cancer treatment, and LPA1 can be a new therapeutic target for highly invasive bladder cancer.

Funding

none