WAVE1 is Associated With Invasiveness and Growth of Prostate Cancer Cells

Purpose

WAVE1 belongs to the Wiskott-Aldrich syndrome family of proteins, which have an integral part in cell motility, a crucial step in cancer metastasis. We investigated the expression pattern and the effects of manipulating endogenous WAVE1 expression in prostate cancer cells.

Materials and Methods

WAVE1 protein expression in normal and cancer specimens, and in prostate cell lines was assessed using immunohistochemistry and reverse transcriptase-polymerase chain reaction, respectively. Hammerhead ribozyme transgenes were synthesized and cloned into the mammalian expression vector pEF6/V5-His TOPO TA, and transfected by electroporation into PC-3^ΔW1R1/2 and DU-145^ΔW1R1/2 cell lines. In vitro invasion, adhesion and growth assays were used to assess the impact of WAVE1 knockdown.

Results

Immunohistochemistry of prostate tissue specimens showed that the cytoplasm of cancer cells had stronger staining than normal epithelium. Reverse transcriptase-polymerase chain reaction for WAVE1 showed strong expression in the PC-3 (European Collection of Cell Cultures, Salisbury, United Kingdom) and DU-145 (ATCC®) cell lines. WAVE1 knockdown was associated with a significant decrease in invasion but not in adhesion. The mean ± SEM number of invading PC-3^ΔW1R1 and PC-3^ΔW1R2 cells was 7.27 ± 0.38 and 6 ± 0.29, respectively, compared to 12.27 ± 0.42 PC-3^WT cells (p <0.001). Similarly the mean number of invading DU-145^ΔW1R1 and DU-145^ΔW1R2 cells was 9.20 ± 0.70 and 11.60 ± 0.84 compared to 14.80 ± 0.24 DU-145^WT cells (p <0.001).

Conclusions

To our knowledge this is the first report of the expression pattern of WAVE1 in prostate cancer cell lines and tissues, and the functional impact of WAVE1 knockdown. Further investigations to assess WAVE1 as a potential target for anti-metastasis therapy must be explored.

Key Words: prostate, prostatic neoplasms, WASF1 protein, human, Wiskott-Aldrich syndrome protein family, neoplasm metastasis

Abbreviations and Acronyms: ECM, extracellular matrix, MMP, matrix metalloproteinase, PCR, polymerase chain reaction, RT-PCR, reverse transcriptase-PCR, WASP, Wiskott-Aldrich syndrome protein, WAVE, WASP family verprolin-homologous protein