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Erschienen in: Clinical & Experimental Metastasis 2/2013

01.02.2013 | Research Paper

Transcriptional profiling identifies genes induced by hepatocyte-derived extracellular matrix in metastatic human colorectal cancer cell lines

verfasst von: Isabel Zvibel, Adam Wagner, Metsada Pasmanik-Chor, Chen Varol, Varda Oron-Karni, Erwin M. Santo, Zamir Halpern, Revital Kariv

Erschienen in: Clinical & Experimental Metastasis | Ausgabe 2/2013

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Abstract

The milieu of the liver, and in particular hepatocyte-derived extracellular matrix (hECM), is a critical factor regulating development of liver metastases of colorectal cancer (CRC) cells. The present study has investigated genes altered by hECM in CRC cells and particularly by heparan sulfate chains of hepatocyte proteoglycans. Gene profiling analysis shows that after 2 days on hECM, 226 genes are up-regulated more than 2-fold in strongly metastatic SM cells, including genes involved in growth arrest and apoptosis, signal transduction, cell migration, proliferation, communication and angiogenesis, with activation of the erbB signaling network and p53 effectors. Genes down-regulated by hECM include genes involved in lipogenesis and the S phase of the cell cycle. Further studies exploring the kinetics of gene expression after 4 and 7 days culture on hECM show induction of EGF family members and of stem cell markers. In particular, hECM, but not collagen, increases mRNA expression of HB-EGF and colon stem cell marker leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5). Expression of these genes is not induced by hECM depleted of the heparan sulfate chains of proteoglycans. Lastly, a specific cell population positive for cancer stem cell (CSC) markers LGR5, epCAM and CD133, but negative for CD44, appears after 7 days culture on hECM, a population which is reduced by 50 % in cells grown on heparan sulfated-depleted hECM. Collectively, the data suggest that hECM induces growth factors and receptors regulating proliferation of metastatic CRC in the liver and offers a growth advantage for specific populations expressing CSC markers.
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Metadaten
Titel
Transcriptional profiling identifies genes induced by hepatocyte-derived extracellular matrix in metastatic human colorectal cancer cell lines
verfasst von
Isabel Zvibel
Adam Wagner
Metsada Pasmanik-Chor
Chen Varol
Varda Oron-Karni
Erwin M. Santo
Zamir Halpern
Revital Kariv
Publikationsdatum
01.02.2013
Verlag
Springer Netherlands
Erschienen in
Clinical & Experimental Metastasis / Ausgabe 2/2013
Print ISSN: 0262-0898
Elektronische ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-012-9527-8

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