PMID- 11073815
OWN - NLM
STAT- MEDLINE
DCOM- 20001207
LR  - 20231105
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 157
IP  - 5
DP  - 2000 Nov
TI  - Expression of c-Met and heparan-sulfate proteoglycan forms of CD44 in colorectal 
      cancer.
PG  - 1563-73
AB  - In colorectal cancer patients, prognosis is not determined by the primary tumor 
      but by the formation of distant metastases. Molecules that have been implicated 
      in the metastatic process are the proto-oncogene product c-Met and CD44 
      glycoproteins. Recently, we obtained evidence for functional collaboration 
      between these two molecules: CD44 isoforms decorated with heparan sulfate chains 
      (CD44-HS) can bind the c-Met ligand, the growth and motility factor hepatocyte 
      growth factor/scatter factor (HGF/SF). This interaction strongly promotes 
      signaling through the receptor tyrosine kinase c-Met. In the present study, we 
      explored the expression of CD44-HS, c-Met, and HGF/SF in the normal human colon 
      mucosa, and in colorectal adenomas and carcinomas, as well as their interaction 
      in colorectal cancer cell lines. Compared to the normal colon, CD44v3 isoforms, 
      which contain a site for HS attachment, and c-Met, were both overexpressed on the 
      neoplastic epithelium of colorectal adenomas and on most carcinomas. Likewise, 
      HGF/SF was expressed at increased levels in tumor tissue. On all tested 
      colorectal cancer cell lines CD44v3 and c-Met were co-expressed. As was shown by 
      immunoprecipitation and Western blotting, CD44 on these cells lines was decorated 
      with HS. Interaction with HS moieties on colorectal carcinoma (HT29) cells 
      promoted HGF/SF-induced activation of c-Met and of the Ras-MAP kinase pathway. 
      Interestingly, survival analysis showed that CD44-HS expression predicts 
      unfavorable prognosis in patients with invasive colorectal carcinomas. Taken 
      together, our findings indicate that CD44-HS, c-Met, and HGF/SF are 
      simultaneously overexpressed in colorectal cancer and that HS moieties promote 
      c-Met signaling in colon carcinoma cells. These observations suggest that 
      collaboration between CD44-HS and the c-Met signaling pathway may play an 
      important role in colorectal tumorigenesis.
FAU - Wielenga, V J
AU  - Wielenga VJ
AD  - Department of Pathology, Academic Medical Center, University of Amsterdam, 
      Amsterdam, The Netherlands.
FAU - van der Voort, R
AU  - van der Voort R
FAU - Taher, T E
AU  - Taher TE
FAU - Smit, L
AU  - Smit L
FAU - Beuling, E A
AU  - Beuling EA
FAU - van Krimpen, C
AU  - van Krimpen C
FAU - Spaargaren, M
AU  - Spaargaren M
FAU - Pals, S T
AU  - Pals ST
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (CD44V3,8-10)
RN  - 0 (Heparan Sulfate Proteoglycans)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Ligands)
RN  - 0 (MAS1 protein, human)
RN  - 0 (Proto-Oncogene Mas)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Colorectal Neoplasms/*metabolism
MH  - Heparan Sulfate Proteoglycans/*metabolism/physiology
MH  - Hepatocyte Growth Factor/metabolism
MH  - Humans
MH  - Hyaluronan Receptors/*metabolism
MH  - Ligands
MH  - Phosphorylation
MH  - Prognosis
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins c-met/*metabolism
PMC - PMC1885727
EDAT- 2000/11/14 11:00
MHDA- 2001/02/28 10:01
PMCR- 2001/05/01
CRDT- 2000/11/14 11:00
PHST- 2000/11/14 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/14 11:00 [entrez]
PHST- 2001/05/01 00:00 [pmc-release]
AID - S0002-9440(10)64793-1 [pii]
AID - 2401 [pii]
AID - 10.1016/S0002-9440(10)64793-1 [doi]
PST - ppublish
SO  - Am J Pathol. 2000 Nov;157(5):1563-73. doi: 10.1016/S0002-9440(10)64793-1.