PMID- 10395325
OWN - NLM
STAT- MEDLINE
DCOM- 19990729
LR  - 20061115
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 5
IP  - 7
DP  - 1999 Jul
TI  - Mammalian heparanase: gene cloning, expression and function in tumor progression 
      and metastasis.
PG  - 793-802
AB  - Heparan sulfate proteoglycans interact with many extracellular matrix
      constituents, growth factors and enzymes. Degradation of heparan sulfate by
      endoglycosidic heparanase cleavage affects a variety of biological processes. We 
      have purified a 50-kDa heparanase from human hepatoma and placenta, and now
      report cloning of the cDNA and gene encoding this enzyme. Expression of the
      cloned cDNA in insect and mammalian cells yielded 65-kDa and 50-kDa recombinant
      heparanase proteins. The 50-kDa enzyme represents an N-terminally processed
      enzyme, at least 100-fold more active than the 65-kDa form. The heparanase mRNA
      and protein are preferentially expressed in metastatic cell lines and specimens
      of human breast, colon and liver carcinomas. Low metastatic murine T-lymphoma and
      melanoma cells transfected with the heparanase cDNA acquired a highly metastatic 
      phenotype in vivo, reflected by a massive liver and lung colonization. This
      represents the first cloned mammalian heparanase, to our knowledge, and provides 
      direct evidence for its role in tumor metastasis. Cloning of the heparanase gene 
      enables the development of specific molecular probes for early detection and
      treatment of cancer metastasis and autoimmune disorders.
FAU - Vlodavsky, I
AU  - Vlodavsky I
AD  - Department of Oncology, Hadassah-Hebrew University Hospital, Jerusalem, Israel.
      vlodavsk@cc.huji.ac.il
FAU - Friedmann, Y
AU  - Friedmann Y
FAU - Elkin, M
AU  - Elkin M
FAU - Aingorn, H
AU  - Aingorn H
FAU - Atzmon, R
AU  - Atzmon R
FAU - Ishai-Michaeli, R
AU  - Ishai-Michaeli R
FAU - Bitan, M
AU  - Bitan M
FAU - Pappo, O
AU  - Pappo O
FAU - Peretz, T
AU  - Peretz T
FAU - Michal, I
AU  - Michal I
FAU - Spector, L
AU  - Spector L
FAU - Pecker, I
AU  - Pecker I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.2.1.- (Glycoside Hydrolases)
RN  - EC 3.2.1.- (heparanase)
RN  - EC 3.2.1.31 (Glucuronidase)
SB  - IM
CIN - Nat Med. 1999 Jul;5(7):735-6. PMID: 10395313
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Carcinoma, Hepatocellular/*enzymology/genetics/pathology
MH  - Cell Line
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 4
MH  - Cloning, Molecular
MH  - Disease Progression
MH  - Enzyme Activation
MH  - Extracellular Matrix/physiology
MH  - Female
MH  - Genomic Library
MH  - *Glucuronidase
MH  - Glycoside Hydrolases/*genetics/isolation & purification/*metabolism
MH  - Humans
MH  - Liver Neoplasms/*enzymology/genetics/pathology
MH  - Mammals
MH  - Mice
MH  - Mice, Inbred DBA
MH  - Molecular Sequence Data
MH  - Molecular Weight
MH  - Moths
MH  - Neoplasm Metastasis/*physiopathology
MH  - Placenta/*enzymology
MH  - Pregnancy
MH  - RNA, Messenger/genetics
MH  - Recombinant Proteins/biosynthesis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcription, Genetic
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 1999/07/08 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/07/08 10:00
PHST- 1999/07/08 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/07/08 10:00 [entrez]
AID - 10.1038/10518 [doi]
PST - ppublish
SO  - Nat Med. 1999 Jul;5(7):793-802. doi: 10.1038/10518.