PMID- 30372043
OWN - NLM
STAT- MEDLINE
DCOM- 20190703
LR  - 20190703
IS  - 1520-4812 (Electronic)
IS  - 1043-1802 (Linking)
VI  - 29
IP  - 11
DP  - 2018 Nov 21
TI  - Properties of Heparinoids Premixed with Tumor-Derived Extracellular Vesicles.
PG  - 3757-3767
LID - 10.1021/acs.bioconjchem.8b00637 [doi]
AB  - Tumor-derived exosomes are bound and internalized to organ-specific cells, 
      affecting metastasis. Heparan sulfate proteoglycans mediate the interaction 
      between cells and exosomes. Exosome transfer to the recipient cell can be 
      competitively blocked by heparinoids, because heparin is structurally similar to 
      heparan sulfate. It is hypothesized that there may be structural requirements of 
      heparinoids to attenuate the cellular uptake and metastatic activity of 
      tumor-derived exosomes. Here, we compared the properties of unfractionated 
      heparin (UFH), glycol-split UFH, low-molecular-weight heparin (LMWH), 
      glycol-split LMWH, and ultra-LMWH premixed with A549-derived exosomes. Uptake of 
      A549-derived exosomes (0.1 mg/mL) into BEAS-2B cells was significantly blocked by 
      0.4 mg/mL of heparinoids. Heparinoids attenuated migration of BEAS-2B cells 
      stimulated by A549-derived exosomes. Glycol-split LMWH with no antifactor Xa 
      activity exhibited the strongest antimigratory effects than other heparinoids. 
      Thus, heparinoids with proper molecular weight and structure can inhibit 
      tumor-derived exosomes, not proportionally to the anticoagulant activity.
FAU - Manandhar, Sumeet
AU  - Manandhar S
FAU - Park, Jooho
AU  - Park J
AD  - Center for Theragnosis, Biomedical Research Institute , Korea Institute of 
      Science and Technology , 5, Hwarang-ro 14-gil , Seongbuk-gu, Seoul 02792 , 
      Republic of Korea.
FAU - Kothandan, Vinoth K
AU  - Kothandan VK
FAU - Lee, Joomin
AU  - Lee J
FAU - Alam, Farzana
AU  - Alam F
AD  - Department of Pharmaceutical Sciences, School of Pharmacy , Texas Tech University 
      Health Sciences Center , Amarillo , Texas 79106 , United States.
FAU - Jee, Jun-Pil
AU  - Jee JP
FAU - Hwang, Jinsu
AU  - Hwang J
FAU - Byun, Youngro
AU  - Byun Y
AUID- ORCID: 0000-0002-3863-2236
AD  - College of Pharmacy , Seoul National University , 1 Gwanak-ro , Gwanak-gu, Seoul 
      08826 , Republic of Korea.
FAU - Hwang, Seung Rim
AU  - Hwang SR
AUID- ORCID: 0000-0002-3250-3396
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181105
PL  - United States
TA  - Bioconjug Chem
JT  - Bioconjugate chemistry
JID - 9010319
RN  - 0 (Anticoagulants)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Heparinoids)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - A549 Cells
MH  - Anticoagulants/chemistry/*pharmacology
MH  - Cell Line
MH  - Exosomes/*drug effects/*metabolism/pathology
MH  - Heparin/chemistry/*pharmacology
MH  - Heparin, Low-Molecular-Weight/chemistry/pharmacology
MH  - Heparinoids/chemistry/pharmacology
MH  - Humans
MH  - Neoplasms/drug therapy/*metabolism/pathology
EDAT- 2018/10/30 06:00
MHDA- 2019/07/04 06:00
CRDT- 2018/10/30 06:00
PHST- 2018/10/30 06:00 [pubmed]
PHST- 2019/07/04 06:00 [medline]
PHST- 2018/10/30 06:00 [entrez]
AID - 10.1021/acs.bioconjchem.8b00637 [doi]
PST - ppublish
SO  - Bioconjug Chem. 2018 Nov 21;29(11):3757-3767. doi: 
      10.1021/acs.bioconjchem.8b00637. Epub 2018 Nov 5.