title: Suppression of invasion and metastasis in aggressive salivary cancer cells through targeted inhibition of ID1 gene expression.
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.
authors.affiliation: 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.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Murase
authors.affiliation: 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.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Sumida
authors.affiliation: California Pacific Medical Center, Cancer Research Institute, 475 Brannan Street, Suite 220, San Francisco, CA 94107, USA.
authors.forename: Rumi
authors.initials: R
authors.lastname: Kawamura
authors.affiliation: Department of Oral & Maxillofacial Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Onishi-Ishikawa
authors.affiliation: Department of Oral & Maxillofacial Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hamakawa
authors.affiliation: California Pacific Medical Center, Cancer Research Institute, 475 Brannan Street, Suite 220, San Francisco, CA 94107, USA.
authors.forename: Sean D
authors.initials: SD
authors.lastname: McAllister
authors.affiliation: California Pacific Medical Center, Cancer Research Institute, 475 Brannan Street, Suite 220, San Francisco, CA 94107, USA. Electronic address: pydesprez@cpmcri.org.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Desprez
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002185:Cannabidiol / Q000494:pharmacology*; D003528:Carcinoma, Adenoid Cystic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D011374:Progesterone / Q000494:pharmacology*; D034622:RNA Interference; D011980:Receptors, Progesterone / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D011980:Receptors, Progesterone; D002185:Cannabidiol; D011374:Progesterone
keywords: Helix–loop–helix; In vivo experiments; Migration; Progesterone; Proliferation