Abstract
Pancreatic adenocarcinoma is an aggressive disease with a high mortality rate. In this study, we have newly generated a monoclonal antibody (mAb), Pa65-2, which specifically binds to pancreatic cancer cells and tumor blood vessels. The target protein of Pa65-2 is identified as human clathrin heavy chain (CHC). In vitro and In vivo study showed that suppression of CHC either by shRNA or by Pa65-2 inhibited tumor growth and angiogenesis. One of the key functions of CHC was to bind with the hypoxia-inducing factor (HIF)-1α protein, increasing the stability of this protein and facilitating its nuclear translocation, thereby regulating the expression of VEGF. Taken together, our findings indicate that CHC plays a role in the processes of tumorigenesis and angiogenesis. Pa65-2 antibody or CHC shRNA can potentially be used for pancreatic cancer therapy.
Original language | English |
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Pages (from-to) | 58-67 |
Number of pages | 10 |
Journal | Cancer Letters |
Volume | 331 |
Issue number | 1 |
DOIs | |
Publication status | Published - Apr 30 2013 |
Externally published | Yes |
Keywords
- Angiogenesis
- Clathrin heavy chain
- HIF-1α
- Monoclonal antibody
- Pancreatic cancer
ASJC Scopus subject areas
- Cancer Research
- Oncology