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Cancer Lett. 2016 Jul 10;377(1):11-6. doi: 10.1016/j.canlet.2016.04.021. Epub 2016 Apr 14.

Suppression of invasion and metastasis in aggressive salivary cancer cells through targeted inhibition of ID1 gene expression.

Author information

1
Department of Oral & Maxillofacial Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan; California Pacific Medical Center, Cancer Research Institute, 475 Brannan Street, Suite 220, San Francisco, CA 94107, USA.
2
California Pacific Medical Center, Cancer Research Institute, 475 Brannan Street, Suite 220, San Francisco, CA 94107, USA.
3
Department of Oral & Maxillofacial Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
4
California Pacific Medical Center, Cancer Research Institute, 475 Brannan Street, Suite 220, San Francisco, CA 94107, USA. Electronic address: pydesprez@cpmcri.org.

Abstract

Salivary gland cancer (SGC) represents the most common malignancy in the head and neck region, and often metastasizes to the lungs. The helix-loop-helix ID1 protein has been shown to control metastatic progression in many types of cancers. Using two different approaches to target the expression of ID1 (genetic knockdown and progesterone receptor introduction combined with progesterone treatment), we previously determined that the aggressiveness of salivary gland tumor ACCM cells in culture was suppressed. Here, using the same approaches to target ID1 expression, we investigated the ability of ACCM cells to generate lung metastatic foci in nude mice. Moreover, since both approaches would be challenging for applications in humans, we added a third approach, i.e., treatment of mice with a non-toxic cannabinoid compound known to down-regulate ID1 gene expression. All approaches aimed at targeting the pro-metastatic ID1 gene led to a significant reduction in the formation of lung metastatic foci. Therefore, targeting a key transcriptional regulator using different means results in the same reduction of the metastatic spread of SGC cells in animal models, suggesting a novel approach for the treatment of patients with aggressive SGC.

KEYWORDS:

Helix–loop–helix; In vivo experiments; Migration; Progesterone; Proliferation

PMID:
27087608
PMCID:
PMC4883028
DOI:
10.1016/j.canlet.2016.04.021
[Indexed for MEDLINE]
Free PMC Article

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