PMID- 28938552
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20170925
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 35
DP  - 2017 Aug 29
TI  - Novel pleiotropic effects of bioactive phospholipids in human lung cancer 
      metastasis.
PG  - 58247-58263
LID - 10.18632/oncotarget.17461 [doi]
AB  - We previously proposed that one of the unwanted side effects of chemotherapy and 
      radiotherapy is the increase in several peptide- and non-peptide based 
      chemoattractants in damaged tissues, leading to induction of a prometastatic 
      microenvironment for remaining cancer cells. Herein, we turned out our attention 
      to a potential role of bioactive phospholipids (BphsLs), such as 
      sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P), 
      lysophosphatidylcholine (LPC), and lysophosphatidic acid (LPA) in lung cancer 
      (LC) metastasis. We report that LC cells express several functional BphL 
      receptors (for S1P, LPC, and LPA) as well as several enzymes involved in their 
      metabolism and that BphsLs are potent chemokinetic and adhesion factors for these 
      cells. We also demonstrate for the first time the novel role of C1P as a 
      prometastatic factor in LC cells. In addition to their chemokinetic activities, 
      BphsLs also sensitize or prime the chemotactic responsiveness of LC cells to 
      known prometastatic factors such as hepatocyte growth factor/scatter factor 
      (HGF/SF). Thus, for the first time we demonstrate a prometastatic effect that is 
      based on the priming of a cell's responsiveness to chemotactic factors by 
      chemokinetic factors. To our surprise, none of the bioactive lipids induced 
      proliferation of LC cells or ameliorated toxic effects of vincristine treatment. 
      Interestingly, BphsLs increase adhesion of LC cells to bone marrow-derived 
      stromal cells and stimulate these cells to release ExNs, which additionally 
      increase LC cell motility. In conclusion, our results show that BphsLs are 
      important modulators of prometastatic environment. Therefore, their inhibitors 
      could be considered as potential anti-metastatic drug candidates to be included 
      as a part of post radio- and/or chemo- therapy treatment.
FAU - Schneider, Gabriela
AU  - Schneider G
AD  - Stem Cell Institute at James Graham Brown Cancer Center, University of 
      Louisville, Louisville, Kentucky, USA.
FAU - Sellers, Zachariah Payne
AU  - Sellers ZP
AD  - Stem Cell Institute at James Graham Brown Cancer Center, University of 
      Louisville, Louisville, Kentucky, USA.
FAU - Bujko, Kamila
AU  - Bujko K
AD  - Stem Cell Institute at James Graham Brown Cancer Center, University of 
      Louisville, Louisville, Kentucky, USA.
FAU - Kakar, Sham S
AU  - Kakar SS
AD  - Department of Physiology and James Graham Brown Cancer Center, University of 
      Louisville, Louisville, Kentucky, USA.
FAU - Kucia, Magda
AU  - Kucia M
AD  - Stem Cell Institute at James Graham Brown Cancer Center, University of 
      Louisville, Louisville, Kentucky, USA.
AD  - Department of Regenerative Medicine, Medical University of Warsaw, Warsaw, 
      Poland.
FAU - Ratajczak, Mariusz Z
AU  - Ratajczak MZ
AD  - Stem Cell Institute at James Graham Brown Cancer Center, University of 
      Louisville, Louisville, Kentucky, USA.
AD  - Department of Regenerative Medicine, Medical University of Warsaw, Warsaw, 
      Poland.
LA  - eng
PT  - Journal Article
DEP - 20170427
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5601648
OTO - NOTNLM
OT  - HGF/SF
OT  - bioactive phospholipids
OT  - lung cancer
OT  - metastasis
OT  - priming
COIS- CONFLICTS OF INTEREST Authors declare no conflicts of interest
EDAT- 2017/09/25 06:00
MHDA- 2017/09/25 06:01
PMCR- 2017/08/29
CRDT- 2017/09/24 06:00
PHST- 2017/03/03 00:00 [received]
PHST- 2017/04/15 00:00 [accepted]
PHST- 2017/09/24 06:00 [entrez]
PHST- 2017/09/25 06:00 [pubmed]
PHST- 2017/09/25 06:01 [medline]
PHST- 2017/08/29 00:00 [pmc-release]
AID - 17461 [pii]
AID - 10.18632/oncotarget.17461 [doi]
PST - epublish
SO  - Oncotarget. 2017 Apr 27;8(35):58247-58263. doi: 10.18632/oncotarget.17461. 
      eCollection 2017 Aug 29.