PMID- 30123360
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240329
IS  - 1837-9664 (Print)
IS  - 1837-9664 (Electronic)
IS  - 1837-9664 (Linking)
VI  - 9
IP  - 16
DP  - 2018
TI  - Stromal mesenchymal stem cells facilitate pancreatic cancer progression by 
      regulating specific secretory molecules through mutual cellular interaction.
PG  - 2916-2929
LID - 10.7150/jca.24415 [doi]
AB  - Pancreatic ductal adenocarcinoma (PDAC) is currently one of the most intractable 
      malignancies with a typical scirrhous pattern in histology. Due to its abundant 
      tumor stroma and scant vascularization, chemotherapeutic agents are considered 
      inefficiently permeable to cancer nests, making it highly difficult to cure the 
      patients with PDAC. However, PDAC is also considered to owe its intractability to 
      other critical factors such as cellular interaction between tumor cells and tumor 
      microenvironment as well as architectural barriers, which increases in 
      therapeutic resistance. Here, we report a specific cellular interaction between 
      PDAC cells and mesenchymal stem cells (MSCs) intermingled in PDAC stroma, which 
      facilitates cancer invasion. Secretory phenotype profiling revealed that 
      production of Amphiregulin (AREG) and MMP-3 were specifically upregulated under 
      the coexistence of BxPC3 cells with human MSCs (approximately four to ten folds 
      in AREG, and twenty to sixty-folds in MMP-3 compared to that of BxPC3 cells 
      alone), whereas MMP-9 expression was decreased (less than one-tenth comparing 
      with that of BxPC3 cells alone). Blockage of AREG production by its specific 
      siRNA removed MSC-mediated driving force of BxPC3 invasiveness. 
      Immunohistochemical analysis of tissue samples obtained both from PDAC patients 
      and PDAC imitating mouse xenografted models revealed that significant 
      coexpression of AREG and its receptor EGFR were detected on the cancer cells at 
      invasive front. These results strongly suggested that cellular interaction 
      between cancer cells and MSCs in the PDAC stroma might be critical to cancer 
      progression, especially in the process of local invasion and the early stage 
      development of metastasis.
FAU - Saito, Ken
AU  - Saito K
AD  - Division of Molecular and Cellular Pathology, Niigata University Graduate School 
      of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, 
      Japan.
FAU - Sakaguchi, Masakiyo
AU  - Sakaguchi M
AD  - Department of Cell Biology, Okayama University Graduate School of Medicine, 
      Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 
      700-8558, Japan.
FAU - Maruyama, Satoshi
AU  - Maruyama S
AD  - Oral Pathology Section, Department of Surgical Pathology, Niigata University 
      Hospital, 2-5274 Gakkoucho-dori, Chuo-ku, Niigata 951-8514, Japan.
FAU - Iioka, Hidekazu
AU  - Iioka H
AD  - Division of Molecular and Cellular Pathology, Niigata University Graduate School 
      of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, 
      Japan.
FAU - Putranto, Endy Widya
AU  - Putranto EW
AD  - Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta 55281.
FAU - Sumardika, I Wayan
AU  - Sumardika IW
AD  - Department of Cell Biology, Okayama University Graduate School of Medicine, 
      Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 
      700-8558, Japan.
AD  - Faculty of Medicine, Udayana University, Denpasar 80232, Bali, Indonesia.
FAU - Tomonobu, Nahoko
AU  - Tomonobu N
AD  - Department of Cell Biology, Okayama University Graduate School of Medicine, 
      Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 
      700-8558, Japan.
FAU - Kawasaki, Takashi
AU  - Kawasaki T
AD  - Department of Pathology, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, 
      Chuo-ku, Niigata 951-8133, Japan.
FAU - Homma, Keiichi
AU  - Homma K
AD  - Department of Pathology, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, 
      Chuo-ku, Niigata 951-8133, Japan.
FAU - Kondo, Eisaku
AU  - Kondo E
AD  - Division of Molecular and Cellular Pathology, Niigata University Graduate School 
      of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, 
      Japan.
LA  - eng
PT  - Journal Article
DEP - 20180730
PL  - Australia
TA  - J Cancer
JT  - Journal of Cancer
JID - 101535920
PMC - PMC6096376
OTO - NOTNLM
OT  - AREG
OT  - MMP
OT  - MSC
OT  - PDAC
OT  - microenvironment
OT  - stroma
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2018/08/21 06:00
MHDA- 2018/08/21 06:01
PMCR- 2018/01/01
CRDT- 2018/08/21 06:00
PHST- 2017/12/17 00:00 [received]
PHST- 2018/07/03 00:00 [accepted]
PHST- 2018/08/21 06:00 [entrez]
PHST- 2018/08/21 06:00 [pubmed]
PHST- 2018/08/21 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - jcav09p2916 [pii]
AID - 10.7150/jca.24415 [doi]
PST - epublish
SO  - J Cancer. 2018 Jul 30;9(16):2916-2929. doi: 10.7150/jca.24415. eCollection 2018.