Download Downregulation of VEGF-C expression in lung and colon cancer

Downregulation of VEGF-C expression in lung and colon cancer cells decelerates
tumor growth and inhibits metastasis via multiple mechanisms
N Khromova, P Kopnin, V Rybko and BP Kopnin
Oncogene (2011) 1–9
Presenter: Ting-chia Chang
Date/Time: 2011/12/08 16:10 -17:00
Commentator: Dr. Nan-Haw Chow
Location: Room 601,Med College Building
Background :
Vascular endothelial growth factor C (VEGF-C) plays an important role in
lymphangiogenesis. VEGF-C binds to Flt4/VEGF receptor 3 (VEGFR3), a receptor
tyrosine kinase that is expressed in the progression of several malignant tumors, including
non-small cell lung cancer, colorectal cancer, and breast carcinoma. In terms of biological
effects, VEGF-C involves in (1) metastasis promotion through lymphangionenesis
induction in tumor tissues and sentinel lymph node spreading and (2) cancer cells
migration. Recent study reported that stimulation of cancer cell motility is partly mediated
by activation of VEGFR3-Src-p38MAPK-C/EBP-contactin-1 pathway. However, both
tumor-promoting mechanism of VEGF-C and the effects of its down-regulation remain
undisclosed. Therefore, both VEGF-C receptor 3-positive A549 lung carcinoma and
HCT116 colon carcinoma cell line with stable repression of VEGF-C expression were
chosen to address these issues in the lung and colon cancer cells.
Objective:
To investigate the biological effects of VEGF-C down-regulation on cell
proliferation and invasion in vitro and inhibition of lymphangiogenesis in vivo.
Results:
Down-regulation of VEGF-C were successfully established in A549 and HCT116
cancer cell lines by lentiviral constructs pLKO.1-shVEGFC (shVEGF-C3 or C-5) as
examined at mRNA and protein levels. The growth of A549 and HCT116 xenografts in
vivo were suppressed after transfection with shVEGF C-3 or C-5. In addition to inhibition
of cell proliferation, migration and tumor lymphangiogenesis, these sublines also exhibited
complex effects of VEGF-C down-regulation. The novel effects observed included partial
reversion of epithelial–mesenchymal transition and a decrease in the percentage of
tumor-initiating cells, also known as ‘cancer stem cells’.
Conclusion:
These results support the potential of VEGF-C as an important drug target in the
design of cancer therapy.
References :
1.
Jen-Liang Su et al. The VEGF-C/Flt-4 axis promotes invasion and metastasis of cancer
cells. CANCER CELL 9, 209–223 (2006)