Invadopodia Are Required for Cancer Cell Extravasation and Are a Therapeutic Target for Metastasis

Hon S. Leong, Amy E. Robertson, Konstantin Stoletov, Sean J. Leith, Curtis A. Chin, Andrew E. Chien, M. Nicole Hague, Amber Ablack, Katia Carmine-Simmen, Victor A. McPherson, CarlO Postenka, Eva A. Turley, Sara Courtneidge, Ann F. Chambers, John D. Lewis

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

Tumor cell extravasation is a key step during cancer metastasis, yet the precise mechanisms that regulate this dynamic process are unclear. We utilized a high-resolution time-lapse intravital imaging approach to visualize the dynamics of cancer cell extravasation invivo. During intravascular migration, cancer cells form protrusive structures identified as invadopodia by their enrichment of MT1-MMP, cortactin, Tks4, and importantly Tks5, which localizes exclusively toinvadopodia. Cancer cells extend invadopodia through the endothelium into the extravascular stroma prior to their extravasation at endothelial junctions. Genetic or pharmacological inhibition of invadopodia initiation (cortactin), maturation (Tks5), or function (Tks4) resulted in an abrogation of cancer cell extravasation and metastatic colony formation in an experimental mouse lung metastasis model. This provides direct evidence of a functional role for invadopodia during cancer cell extravasation and distant metastasis and reveals an opportunity for therapeutic intervention in this clinically important process.

Original languageEnglish (US)
Pages (from-to)1558-1570
Number of pages13
JournalCell Reports
Volume8
Issue number5
DOIs
StatePublished - 2014

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Cells
Neoplasm Metastasis
Cortactin
Neoplasms
Therapeutics
Matrix Metalloproteinase 14
Time-Lapse Imaging
Podosomes
Tumors
Endothelium
Imaging techniques
Pharmacology
Lung

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Leong, H. S., Robertson, A. E., Stoletov, K., Leith, S. J., Chin, C. A., Chien, A. E., ... Lewis, J. D. (2014). Invadopodia Are Required for Cancer Cell Extravasation and Are a Therapeutic Target for Metastasis. Cell Reports, 8(5), 1558-1570. https://doi.org/10.1016/j.celrep.2014.07.050

Invadopodia Are Required for Cancer Cell Extravasation and Are a Therapeutic Target for Metastasis. / Leong, Hon S.; Robertson, Amy E.; Stoletov, Konstantin; Leith, Sean J.; Chin, Curtis A.; Chien, Andrew E.; Hague, M. Nicole; Ablack, Amber; Carmine-Simmen, Katia; McPherson, Victor A.; Postenka, CarlO; Turley, Eva A.; Courtneidge, Sara; Chambers, Ann F.; Lewis, John D.

In: Cell Reports, Vol. 8, No. 5, 2014, p. 1558-1570.

Research output: Contribution to journalArticle

Leong, HS, Robertson, AE, Stoletov, K, Leith, SJ, Chin, CA, Chien, AE, Hague, MN, Ablack, A, Carmine-Simmen, K, McPherson, VA, Postenka, C, Turley, EA, Courtneidge, S, Chambers, AF & Lewis, JD 2014, 'Invadopodia Are Required for Cancer Cell Extravasation and Are a Therapeutic Target for Metastasis', Cell Reports, vol. 8, no. 5, pp. 1558-1570. https://doi.org/10.1016/j.celrep.2014.07.050
Leong, Hon S. ; Robertson, Amy E. ; Stoletov, Konstantin ; Leith, Sean J. ; Chin, Curtis A. ; Chien, Andrew E. ; Hague, M. Nicole ; Ablack, Amber ; Carmine-Simmen, Katia ; McPherson, Victor A. ; Postenka, CarlO ; Turley, Eva A. ; Courtneidge, Sara ; Chambers, Ann F. ; Lewis, John D. / Invadopodia Are Required for Cancer Cell Extravasation and Are a Therapeutic Target for Metastasis. In: Cell Reports. 2014 ; Vol. 8, No. 5. pp. 1558-1570.
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