File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
  • Find via Find It@HKUL
Supplementary

Conference Paper: Blockade of chemokine receptor CXCR4 for the treatment of hepatocellular carcinoma metastasis

TitleBlockade of chemokine receptor CXCR4 for the treatment of hepatocellular carcinoma metastasis
Authors
Issue Date2007
PublisherAmerican Association for Cancer Research
Citation
AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, San Francisco, CA, 22–26 October, 2007. In Molecular Cancer Therapeutics, 2007, v. 6 n.11S, p. B223 How to Cite?
AbstractBackground Hepatocellular carcinoma (HCC) is one of the five most common cancers worldwide. The prognosis of HCC is poor and the metastatic rate is high in HCC patients. However, the mechanism of HCC metastasis remains largely unclear. Here we investigated the potential role of SDF-1 and its receptor, Chemokine (C-X-C motif) receptor 4 (CXCR4), in HCC metastasis and explored the therapeutic potential of CXCR4 blockade for the treatment of HCC metastasis. Methods and Results This study included three parts. In vitro, higher levels of CXCR4 expression were detected in metastatic HCC cell lines (MHCC 97H and MHCC 97L) than non-metastatic cell line (PLC) by western blot, flow cytometry, and immuno-fluorescent staining. Interestingly, metastatic cell lines secreted lower levels of SDF-1 into the culture medium than non-metastatic cells. SDF-1 up-regulated adhesion molecule ICAM-1, induced filapodia formation and stimulated the chemotaxis of MHCC97L and MHCC97H cells. Blockade of CXCR4 activity by CXCR4 antagonist, CTCE-9908 (Chemokine Therapeutics Corp.) inhibited SDF-1 mediated migration of MHCC97L and MHCC97H cells at 5 µM. On the other hand, CTCE-9908 suppressed proliferation of tumor cells and induced cell apoptosis with doses higher than 100 μM. In contrast, CTCE-9908 did not arrest cell cycle progression even at the highest doses. In vivo, an orthotopic HCC model was induced by injection of MHCC97L cells into the left lobe of the liver of nude mice and the tumor-bearing mice were treated with CTCE-9908 for 6 weeks. Administration of CTCE-9908 subcutaneously significantly decreased the number of circulating tumour cells and decreased the number of metastatic tumor nodules in the lung. A mild inhibitory effect on tumor growth was also observed with CTCE-9908 treatment. The expression of CXCR4 in human HCC tumor and non-tumorous tissues was investigated by immunohistochemisty. CXCR4 was highly expressed in tumour tissues with different staining patterns. Diffused nuclear and cytoplasmic staining was identified in the non-metastatic tumor tissues, while strong nuclear staining only was detected in the tumor tissues with secondary lung metastasis. ConclusionSDF-1/CXCR4 axis plays an important role in the migration and metastasis of HCC. Blockade of SDF-1/CXCR4 interaction is a potential therapeutic strategy for the treatment of HCC metastasis.
Persistent Identifierhttp://hdl.handle.net/10722/108058
ISSN
2015 Impact Factor: 5.579
2015 SCImago Journal Rankings: 3.224

 

DC FieldValueLanguage
dc.contributor.authorKok, TWen_HK
dc.contributor.authorYang, Zen_HK
dc.contributor.authorPoon, RTPen_HK
dc.date.accessioned2010-09-26T00:23:42Z-
dc.date.available2010-09-26T00:23:42Z-
dc.date.issued2007en_HK
dc.identifier.citationAACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, San Francisco, CA, 22–26 October, 2007. In Molecular Cancer Therapeutics, 2007, v. 6 n.11S, p. B223-
dc.identifier.issn1535-7163-
dc.identifier.urihttp://hdl.handle.net/10722/108058-
dc.description.abstractBackground Hepatocellular carcinoma (HCC) is one of the five most common cancers worldwide. The prognosis of HCC is poor and the metastatic rate is high in HCC patients. However, the mechanism of HCC metastasis remains largely unclear. Here we investigated the potential role of SDF-1 and its receptor, Chemokine (C-X-C motif) receptor 4 (CXCR4), in HCC metastasis and explored the therapeutic potential of CXCR4 blockade for the treatment of HCC metastasis. Methods and Results This study included three parts. In vitro, higher levels of CXCR4 expression were detected in metastatic HCC cell lines (MHCC 97H and MHCC 97L) than non-metastatic cell line (PLC) by western blot, flow cytometry, and immuno-fluorescent staining. Interestingly, metastatic cell lines secreted lower levels of SDF-1 into the culture medium than non-metastatic cells. SDF-1 up-regulated adhesion molecule ICAM-1, induced filapodia formation and stimulated the chemotaxis of MHCC97L and MHCC97H cells. Blockade of CXCR4 activity by CXCR4 antagonist, CTCE-9908 (Chemokine Therapeutics Corp.) inhibited SDF-1 mediated migration of MHCC97L and MHCC97H cells at 5 µM. On the other hand, CTCE-9908 suppressed proliferation of tumor cells and induced cell apoptosis with doses higher than 100 μM. In contrast, CTCE-9908 did not arrest cell cycle progression even at the highest doses. In vivo, an orthotopic HCC model was induced by injection of MHCC97L cells into the left lobe of the liver of nude mice and the tumor-bearing mice were treated with CTCE-9908 for 6 weeks. Administration of CTCE-9908 subcutaneously significantly decreased the number of circulating tumour cells and decreased the number of metastatic tumor nodules in the lung. A mild inhibitory effect on tumor growth was also observed with CTCE-9908 treatment. The expression of CXCR4 in human HCC tumor and non-tumorous tissues was investigated by immunohistochemisty. CXCR4 was highly expressed in tumour tissues with different staining patterns. Diffused nuclear and cytoplasmic staining was identified in the non-metastatic tumor tissues, while strong nuclear staining only was detected in the tumor tissues with secondary lung metastasis. ConclusionSDF-1/CXCR4 axis plays an important role in the migration and metastasis of HCC. Blockade of SDF-1/CXCR4 interaction is a potential therapeutic strategy for the treatment of HCC metastasis.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research-
dc.relation.ispartofMolecular Cancer Therapeuticsen_HK
dc.titleBlockade of chemokine receptor CXCR4 for the treatment of hepatocellular carcinoma metastasisen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailYang, Z: zfyang@hkucc.hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hken_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.hkuros139184en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats