title: Extravasation during bladder cancer metastasis requires cortactin‑mediated invadopodia formation.
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.
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036‑8562, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Tokui
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036‑8562, Japan.
authors.forename: Mihoko Sutoh
authors.initials: MS
authors.lastname: Yoneyama
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036‑8562, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Hatakeyama
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036‑8562, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036‑8562, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Koie
authors.affiliation: Department of Urology, Oyokyo Kidney Research Institute, Hirosaki, Aomori 036‑8243, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Saitoh
authors.affiliation: Department of Urology, Oyokyo Kidney Research Institute, Hirosaki, Aomori 036‑8243, Japan.
authors.forename: Kanemitsu
authors.initials: K
authors.lastname: Yamaya
authors.affiliation: Department of Urology, Oyokyo Kidney Research Institute, Hirosaki, Aomori 036‑8243, Japan.
authors.forename: Tomihisa
authors.initials: T
authors.lastname: Funyu
authors.affiliation: Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036‑8564, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036‑8562, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Ohyama
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036‑8562, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tsuboi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D051356:Cortactin / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D011554:Pseudopodia / Q000378:metabolism* / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*
chemical_list: C495868:CTTN protein, human; D051356:Cortactin; D020782:Matrix Metalloproteinases