PMID- 27725845
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1943-8141 (Print)
IS  - 1943-8141 (Electronic)
IS  - 1943-8141 (Linking)
VI  - 8
IP  - 9
DP  - 2016
TI  - Exosome mediated growth effect on the non-growing pre-B acute lymphoblastic 
      leukemia cells at low starting cell density.
PG  - 3614-3629
AB  - Tumors contain heterogeneous cell populations and achieve dominance by 
      functioning as collective systems. The mechanisms underlying the aberrant growth 
      and interactions between cells are not very well understood. The pre-B acute 
      lymphoblastic leukemia cells we studied were obtained directly from a patient 
      with Ph+ ALL. A new Ph+ ALL cell line (ALL3) was established from the leukemic 
      cells growing as ascitic cells in his pleural fluid. The patient died of his 
      disease shortly after the cells were obtained. ALL3 cells grow well at high cell 
      densities (HD), but not at low cell densities. ALL3 cells are very sensitive to 
      potent tyrosine kinase inhibitors (TKIs) such as Dasatinib and PD166325, but less 
      sensitive to AMN 107, Imatinib, and BMS 214662 (a farnesyl transferase 
      inhibitor). Here, we show that the growth of the LD ALL3 cells can be stimulated 
      to grow in the presence of diffusible, soluble factors secreted by ALL3 cells 
      themselves growing at high density. We also show that exosomes, part of the 
      secretome components, are also able to stimulate the growth of the non-growing LD 
      ALL3 cells and modulate their proliferative behavior. Characterization of the 
      exosome particles also showed that the HD ALL3 cells are able to secret them in 
      large quantities and that they are capable of inducing the growth of the LD ALL3 
      cells without which they will not survive. Direct stimulation of non-growing LD 
      ALL3 cells using purified exosomes shows that the ALL3 cells can also communicate 
      with each other by means of exchange of exosomes independently of direct 
      cell-cell contacts or diffusible soluble stimulatory factors secreted by HD ALL3 
      cells.
FAU - Patel, Sapan J
AU  - Patel SJ
AD  - Memorial Sloan Kettering Cancer Center, Molecular Pharmacology Program1275 York 
      Avenue, Box #96, New York, NY 10065, USA; Clarkson University, Biochemistry and 
      Proteomics Group, Department of Chemistry and Bio-molecular Science, Clarkson 
      University8 Clarkson Avenue, Potsdam, NY, 13699-5810, USA.
FAU - Darie, Costel C
AU  - Darie CC
AD  - Clarkson University, Biochemistry and Proteomics Group, Department of Chemistry 
      and Bio-molecular Science, Clarkson University 8 Clarkson Avenue, Potsdam, NY, 
      13699-5810, USA.
FAU - Clarkson, Bayard D
AU  - Clarkson BD
AD  - Memorial Sloan Kettering Cancer Center, Molecular Pharmacology Program 1275 York 
      Avenue, Box #96, New York, NY 10065, USA.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20160915
PL  - United States
TA  - Am J Transl Res
JT  - American journal of translational research
JID - 101493030
PMC - PMC5040663
OTO - NOTNLM
OT  - Acute lymphoblastic leukemia
OT  - collective behavior
OT  - exosome
OT  - proliferation
OT  - quorum sensing
OT  - tyrosine kinase inhibitor
EDAT- 2016/10/12 06:00
MHDA- 2016/10/12 06:01
PMCR- 2016/09/15
CRDT- 2016/10/12 06:00
PHST- 2016/07/26 00:00 [received]
PHST- 2016/08/30 00:00 [accepted]
PHST- 2016/10/12 06:00 [entrez]
PHST- 2016/10/12 06:00 [pubmed]
PHST- 2016/10/12 06:01 [medline]
PHST- 2016/09/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Transl Res. 2016 Sep 15;8(9):3614-3629. eCollection 2016.