PMID- 28642617
OWN - NLM
STAT- MEDLINE
DCOM- 20181231
LR  - 20181231
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Jun 22
TI  - Podoplanin enhances lung cancer cell growth in vivo by inducing platelet 
      aggregation.
PG  - 4059
LID - 10.1038/s41598-017-04324-1 [doi]
LID - 4059
AB  - Podoplanin/Aggrus, known as a platelet aggregation-inducing factor, is frequently 
      overexpressed in lung squamous cell carcinomas (LSCC) and glioblastomas among 
      other tumours, and its expression has been reported to be correlated with poor 
      prognosis. However, the contribution of podoplanin to malignant progression has 
      been elusive. Here we demonstrate that in podoplanin-positive LSCC cells, their 
      growth was abrogated by podoplanin knockout in vivo but not in vitro. Conversely, 
      ectopic expression of podoplanin promoted cell growth in vivo and facilitated 
      intratumoral platelet activation. Consistently, LSCC cells evoked 
      podoplanin-mediated platelet aggregation (PMPA), and the releasates from 
      platelets during PMPA promoted the growth of LSCC cells in vitro. 
      Phospho-receptor-tyrosine-kinase array analysis revealed that epidermal growth 
      factor receptor (EGFR) phosphorylation of LSCC cells was responsible for the 
      growth promotion induced by platelet releasates. Treatment with an antiplatelet 
      agent or podoplanin-neutralizing antibody depressed the growth of an LSCC tumour 
      xenograft via suppression of EGFR phosphorylation. These results suggested that 
      podoplanin in LSCC enhanced cell growth by inducing PMPA in vivo and contributed 
      to malignant progression.
FAU - Miyata, Kenichi
AU  - Miyata K
AD  - Division of Experimental Chemotherapy, The Cancer Chemotherapy Center, Japanese 
      Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan.
AD  - Department of Computational Biology and Medical Sciences, Graduate School of 
      Frontier Sciences, The University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa-shi, 
      Chiba, 277-8561, Japan.
FAU - Takemoto, Ai
AU  - Takemoto A
AD  - Division of Experimental Chemotherapy, The Cancer Chemotherapy Center, Japanese 
      Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan.
FAU - Okumura, Sakae
AU  - Okumura S
AD  - Thoracic Oncology Center, Cancer Institute Hospital, Japanese Foundation for 
      Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 1350-8550, Japan.
FAU - Nishio, Makoto
AU  - Nishio M
AD  - Thoracic Oncology Center, Cancer Institute Hospital, Japanese Foundation for 
      Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 1350-8550, Japan.
FAU - Fujita, Naoya
AU  - Fujita N
AD  - Division of Experimental Chemotherapy, The Cancer Chemotherapy Center, Japanese 
      Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan. 
      naoya.fujita@jfcr.or.jp.
AD  - Department of Computational Biology and Medical Sciences, Graduate School of 
      Frontier Sciences, The University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa-shi, 
      Chiba, 277-8561, Japan. naoya.fujita@jfcr.or.jp.
AD  - The Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31, 
      Ariake, Koto-ku, Tokyo, 135-8550, Japan. naoya.fujita@jfcr.or.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170622
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Biomarkers)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (PDPN protein, human)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Animals
MH  - Biomarkers
MH  - Blood Platelets/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Disease Models, Animal
MH  - ErbB Receptors/antagonists & inhibitors/metabolism
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Lung Neoplasms/*blood/*metabolism
MH  - Membrane Glycoproteins/*metabolism/pharmacology
MH  - Mice
MH  - *Platelet Aggregation/drug effects
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Signal Transduction/drug effects
MH  - Xenograft Model Antitumor Assays
PMC - PMC5481446
COIS- The authors declare that they have no competing interests.
EDAT- 2017/06/24 06:00
MHDA- 2019/01/01 06:00
PMCR- 2017/06/22
CRDT- 2017/06/24 06:00
PHST- 2016/09/09 00:00 [received]
PHST- 2017/05/12 00:00 [accepted]
PHST- 2017/06/24 06:00 [entrez]
PHST- 2017/06/24 06:00 [pubmed]
PHST- 2019/01/01 06:00 [medline]
PHST- 2017/06/22 00:00 [pmc-release]
AID - 10.1038/s41598-017-04324-1 [pii]
AID - 4324 [pii]
AID - 10.1038/s41598-017-04324-1 [doi]
PST - epublish
SO  - Sci Rep. 2017 Jun 22;7(1):4059. doi: 10.1038/s41598-017-04324-1.