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Cell Rep. 2014 Sep 11;8(5):1558-70. doi: 10.1016/j.celrep.2014.07.050. Epub 2014 Aug 28.

Invadopodia are required for cancer cell extravasation and are a therapeutic target for metastasis.

Author information

1
Translational Prostate Cancer Research Group, London Regional Cancer Program, 790 Commissioners Road East, London ON N6A 4L6, Canada.
2
Department of Oncology, University of Alberta, 5-142C Katz Group Building, Edmonton AB T6G 2E1, Canada.
3
London Regional Cancer Program, Cancer Research Laboratory Program, 790 Commissioners Road East, London ON N6A 4L6, Canada.
4
London Regional Cancer Program, Cancer Research Laboratory Program, 790 Commissioners Road East, London ON N6A 4L6, Canada; Departments of Biochemistry, Oncology, and Surgery, Western University, London, ON N6A 5C1, Canada.
5
Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Collaborative Life Sciences Building, 2750 SW Moody Avenue, Portland, OR 97239, USA.
6
Department of Oncology, University of Alberta, 5-142C Katz Group Building, Edmonton AB T6G 2E1, Canada. Electronic address: jdlewis@ualberta.ca.

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 in vivo. 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 to invadopodia. 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.

PMID:
25176655
DOI:
10.1016/j.celrep.2014.07.050
[Indexed for MEDLINE]
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