Extravasation during bladder cancer metastasis requires cortactin‑mediated invadopodia formation

Tokui,Noriko; Yoneyama,Mihoko Sutoh; Hatakeyama,Shingo; Yamamoto,Hayato; Koie,Takuya; Saitoh,Hisao; Yamaya,Kanemitsu; Funyu,Tomihisa; Nakamura,Toshiya; Ohyama,Chikara; Tsuboi,Shigeru

doi:10.3892/mmr.2014.1965

Extravasation during bladder cancer metastasis requires cortactin‑mediated invadopodia formation

Authors:
- Noriko Tokui
- Mihoko Sutoh Yoneyama
- Shingo Hatakeyama
- Hayato Yamamoto
- Takuya Koie
- Hisao Saitoh
- Kanemitsu Yamaya
- Tomihisa Funyu
- Toshiya Nakamura
- Chikara Ohyama
- Shigeru Tsuboi
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Affiliations: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036‑8562, Japan, Department of Urology, Oyokyo Kidney Research Institute, Hirosaki, Aomori 036‑8243, Japan, Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036‑8564, Japan
Published online on: February 19, 2014 https://doi.org/10.3892/mmr.2014.1965
Pages: 1142-1146

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Abstract

Invasive cancer cells form the filamentous actin‑based membrane protrusions known as invadopodia. Invadopodia are thought to play a critical role in cancer cell invasion and metastasis due to their ability to degrade the extracellular matrix. The present study assessed whether invadopodia formation is essential in extravasation of circulating bladder cancer cells and lung metastasis. To analyze the importance of invadopodia, bladder cancer cell lines with reduced invadopodia formation were established by silencing the expression of cortactin, an essential component of invadopodia, using cortactin short hairpin RNA. Bladder cancer cells with cortactin knockdown demonstrated a markedly decreased ability to form invadopodia, secrete matrix metalloproteinases and invade the extracellular matrix. In addition, the knockdown cells exhibited a reduced transendothelial invasion capacity and decreased formation of metastatic foci in the lungs. The present study demonstrated that bladder cancer cells with cortactin knockdown have a reduced capacity to extravasate into the lung from the circulation, due to the decreased invasive character of invadopodia. This suggests that invadopodia formation is a critical process for cancer cell extravasation.

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