Pancreatic Fibroblasts Stimulate the Motility of Pancreatic Cancer Cells through IGF1/IGF1R Signaling under Hypoxia
Publication Date
August 03, 2016
Journal
PLOS ONE
Authors
Toshiki Hirakawa, Masakazu Yashiro, Yosuke Doi, Haruhito Kinoshita, et al
Volume
11
Issue
8
Pages
e0159912
DOI
https://dx.plos.org/10.1371/journal.pone.0159912
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0159912
Scopus
84982299423
Mendeley
http://www.mendeley.com/research/pancreatic-fibroblasts-stimulate-motility-pancreatic-cancer-cells-through-igf1igf1r-signaling-under
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Mendeley | Further Information

{"title"=>"Pancreatic fibroblasts stimulate the motility of pancreatic cancer cells through IGF1/IGF1R signaling under hypoxia", "type"=>"journal", "authors"=>[{"first_name"=>"Toshiki", "last_name"=>"Hirakawa", "scopus_author_id"=>"35753126100"}, {"first_name"=>"Masakazu", "last_name"=>"Yashiro", "scopus_author_id"=>"7006654058"}, {"first_name"=>"Yosuke", "last_name"=>"Doi", "scopus_author_id"=>"26022252300"}, {"first_name"=>"Haruhito", "last_name"=>"Kinoshita", "scopus_author_id"=>"56332665800"}, {"first_name"=>"Tamami", "last_name"=>"Morisaki", "scopus_author_id"=>"36439793000"}, {"first_name"=>"Tatsunari", "last_name"=>"Fukuoka", "scopus_author_id"=>"35603266400"}, {"first_name"=>"Tsuyoshi", "last_name"=>"Hasegawa", "scopus_author_id"=>"51664746100"}, {"first_name"=>"Kenjiro", "last_name"=>"Kimura", "scopus_author_id"=>"55728467800"}, {"first_name"=>"Ryosuke", "last_name"=>"Amano", "scopus_author_id"=>"24079830300"}, {"first_name"=>"Kosei", "last_name"=>"Hirakawa", "scopus_author_id"=>"7202127012"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "sgr"=>"84982299423", "scopus"=>"2-s2.0-84982299423", "pui"=>"611683630", "doi"=>"10.1371/journal.pone.0159912", "pmid"=>"27487118"}, "id"=>"b3f6031e-bb3f-39b7-b85b-c4f15bf08250", "abstract"=>"Pancreatic ductal adenocarcinoma (PDAC) is characterized by its hypovascularity, with an extremely poor prognosis because of its highly invasive nature. PDAC proliferates with abundant stromal cells, suggesting that its invasive activity might be controlled by intercellular interactions between cancer cells and fibroblasts. Using four PDAC cell lines and two pancreas cancer-associated fibroblasts (CAFs), the expression of insulin-like growth factor-1 (IGF1) and IGF1 receptor (IGF1R) was evaluated by RT-PCR, FACScan, western blot, or ELISA. Correlation between IGF1R and the hypoxia marker carbonic anhydrase 9 (CA9) was examined by immunohistochemical staining of 120 pancreatic specimens. The effects of CAFs, IGF1, and IGF1R inhibitors on the motility of cancer cells were examined by wound-healing assay or invasion assay under normoxia (20% O2) and hypoxia (1% O2). IGF1R expression was significantly higher in RWP-1, MiaPaCa-2, and OCUP-AT cells than in Panc-1 cells. Hypoxia increased the expression level of IGF1R in RWP-1, MiaPaCa-2, and OCUP-AT cells. CA9 expression was correlated with IGF1R expression in pancreatic specimens. CAFs produced IGF1 under hypoxia, but PDAC cells did not. A conditioned medium from CAFs, which expressed αSMA, stimulated the migration and invasion ability of MiaPaCa-2, RWP-1, and OCUP-AT cells. The motility of all PDAC cells was greater under hypoxia than under normoxia. The motility-stimulating ability of CAFs was decreased by IGF1R inhibitors. These findings might suggest that pancreas CAFs stimulate the invasion activity of PDAC cells through paracrine IGF1/IGF1R signaling, especially under hypoxia. Therefore the targeting of IGF1R signaling might represent a promising therapeutic approach in IGF1R-dependent PDAC.", "link"=>"http://www.mendeley.com/research/pancreatic-fibroblasts-stimulate-motility-pancreatic-cancer-cells-through-igf1igf1r-signaling-under", "reader_count"=>15, "reader_count_by_academic_status"=>{"Researcher"=>3, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Researcher"=>3, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>0}

Scopus | Further Information

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