Invasive carcinoma cells acquire a migratory phenotype associated with an increased expression of several genes involved in cell motility (1). WASP(Wiskott-Aldrich Syndrome Protein), (N)-WASP and WAVE(WASP family verprolin-homologous protein)proteins are thought to play a role in signal dependent regulation of actin dynamics, which in turn is essential for a variety of cellular processes including the formation of membrane protrusions- the first step in cell motility. Evidence suggests that some members of the CCN family (for e.g. Cyr61, CTGF and Nov) stimulate mitosis, adhesion, apoptosis, growth arrest and migration of multiple cell types including prostate cancer. Other CCN members, namely WISPs also play a role in the invasiveness of prostate cancer cells (2). Not much data exists in literature about the expression of WAVE’s - also members of the CCN family, in prostate cancers. Here we report findings from a pilot study done to investigate the expression of WAVEs in prostate cancers.
Materials and Methods:
LNCaP, DU-145, PC-3, CaHPV, PZHPV, PNT1A and PNT2C2 were used in the study. Conventional RT-PCR was used to detect expression of the WAVE1-3 transcripts and β-actin and GAPDH were used as house keeping genes. Using immunohistochemical methods, a panel of prostate tissues which were earlier frozen-sectioned were stained for WAVE-1, -2 and -3 and later analysed for their expression using conventional RT-PCR.
Human prostate cancer cell lines showed a diverse pattern of expression of the three CCN members. WAVE-1 transcripts were found in most of the prostate cancer cell lines in both highly invasive and non-invasive cells. While PC-3 and DU145 cells showed a low level of WAVE-2 transcripts, non-invasive LN-CaP and CA-HPV showed good levels. Similarly, LNCaP, PNT1A and CA-HPV showed a strong positive signal to WAVE-3 expression and moderate expression in others. All three WAVEs were seen to be stained in normal human prostate epithelial cells, with WAVE-1 being the strongest and WAVE-3 the weakest. Interestingly, there was a visible reduction of WAVE-2 staining in tumour cells of the prostate tissues.
We conclude from this preliminary study that WAVE’s have a differential expression pattern in human prostate cancer cell lines, which may have some link to the pattern of cell invasion and motility. Further studies are currently being undertaken in order to identify the molecular impact of WAVEs on the biological behaviour of prostate cancer cell lines.
1. Hawizy A, Davies G, Mason MD, Kynaston H, Jiang WG. The role of WISPs in human prostate cancer. Presented at Prostate Cancer Symposium, ASCO, Feb. 2005, Orlando, Florida, US
2. Yamaguchi H et al. Cell Migration in tumors. Current opinion in Cell Biology 2005, 17:559-564
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA