Invadopodia play a role in prostate cancer progression

Valeria Manuelli, Fidelma Cahill, Harriet Wylie, Cheryl Gillett, Isabel Correa, Susanne Heck, Alex Rimmer, Anna Haire, Mieke Van Hemelrijck, Sarah Rudman, Claire Wells*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)
46 Downloads (Pure)

Abstract

Background: Invadopodia, actin-rich structures that release metallo-proteases at the interface with extra-cellular matrix, in a punctate manner are thought to be important drivers of tumour invasion. Invadopodia formation has been observed in-vitro and in-vivo in numerous metastatic cell lines derived from multiple tumour types. However, prostate cancer cell lines have not been routinely reported to generate invadopodia and the few instances have always required external stimulation. Methods: In this study, the invasive potential of primary prostate adenocarcinoma cell lines, which have never been fully characterised before, was investigated both in-vitro invadopodia assays and in-vivo zebrafish dissemination assay. Subsequently, circulating tumour cells from prostate cancer patients were isolated and tested in the invadopodia assay. Results: Retention of E-cadherin and N-cadherin expression indicated a transitional state of EMT progression, consistent with the idea of partial EMT that has been frequently observed in aggressive prostate cancer. All cell lines tested were capable of spontaneous invadopodia formation and possess a significant degradative ability in-vitro under basal conditions. These cell lines were invasive in-vivo and produced visible metastasis in the zebrafish dissemination assay. Importantly we have proceeded to demonstrate that circulating tumour cells isolated from prostate cancer patients exhibit invadopodia-like structures and degrade matrix with visible puncta. This work supports a role for invadopodia activity as one of the mechanisms of dissemination employed by prostate cancer cells. Conclusion: The combination of studies presented here provide clear evidence that invadopodia activity can play a role in prostate cancer progression.

Original languageEnglish
Article number386
JournalBMC Cancer
Volume22
Issue number1
DOIs
Publication statusAccepted/In press - 16 Mar 2022

Keywords

  • Invadopodia
  • Prostate cancer
  • CTC

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