PMID- 24138671
OWN - NLM
STAT- MEDLINE
DCOM- 20140623
LR  - 20211021
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 13
DP  - 2013 Oct 20
TI  - Endothelial cells do not arise from tumor-initiating cells in human 
      hepatocellular carcinoma.
PG  - 485
LID - 10.1186/1471-2407-13-485 [doi]
AB  - BACKGROUND: Conventional models of carcinogenesis suggest that tumors recruit 
      blood vessel formation from normal host tissues. This concept has recently been 
      challenged by prominent studies of glioblastoma, which suggest that intratumoral 
      endothelial cells (ECs) may arise from cancer stem cells/tumor-initiating cells 
      (TICs). Hepatocellular carcinoma (HCC) is a common, highly vascularized tumor 
      with few effective therapies, against which anti-angiogenic strategies are being 
      actively explored. TICs are felt to play a role in HCC pathobiology, but their 
      contributions to tumor vasculature have not been studied. METHODS: We examined 
      human HCCs in settings that selected for tumor formation from functionally 
      defined TICs, and in which the origin of intratumoral ECs from TICs as opposed to 
      host tissues could be clearly distinguished. We generated HCC nodules in the 
      livers of immunodeficient mice by intrasplenic injection of HCC cells from cell 
      lines and patient specimens and studied the tumor ECs by immunohistochemistry for 
      mouse and human markers. We then used immunohistochemistry for EC markers in 
      combination with fluorescence in situ hybridization (FISH) for X and Y 
      chromosomes to study the endothelium of recurrent HCC specimens resected from 
      sex-mismatched liver allografts of patients who had undergone liver 
      transplantation for HCC. RESULTS: We observed that all ECs in intrahepatic human 
      HCC xenografts expressed mouse rather than human CD31. FISH analysis of recurrent 
      HCCs resected from patients with sex-mismatched liver allografts revealed that 
      all CD31+ and CD34+ intratumoral ECs originated from the donor allograft rather 
      than the tumor. CONCLUSIONS: These observations suggest that the vasculature of 
      human HCC arises from normal host tissues rather than from TICs, supporting 
      ongoing efforts to target angiogenesis in HCC as it is currently understood, and 
      suggesting that the contribution of TICs to the vasculature of other cancers is 
      disease-specific.
FAU - Ghanekar, Anand
AU  - Ghanekar A
AD  - Toronto General Research Institute, University Health Network, Toronto, ON, 
      Canada. anand.ghanekar@uhn.ca.
FAU - Ahmed, Sharif
AU  - Ahmed S
FAU - Chen, Kui
AU  - Chen K
FAU - Adeyi, Oyedele
AU  - Adeyi O
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131020
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Platelet Endothelial Cell Adhesion Molecule-1)
SB  - IM
MH  - Animals
MH  - Carcinoma, Hepatocellular/diagnosis/metabolism/*pathology/therapy
MH  - Cell Line, Tumor
MH  - Disease Models, Animal
MH  - Endothelial Cells/metabolism/*pathology
MH  - Female
MH  - Heterografts
MH  - Humans
MH  - Liver/metabolism/pathology
MH  - Liver Neoplasms/diagnosis/metabolism/*pathology/therapy
MH  - Liver Transplantation
MH  - Magnetic Resonance Imaging
MH  - Mice
MH  - Neoplasm Recurrence, Local
MH  - Neoplastic Stem Cells/metabolism/*pathology
MH  - Platelet Endothelial Cell Adhesion Molecule-1/metabolism
MH  - Transplantation, Homologous
PMC - PMC3856592
EDAT- 2013/10/22 06:00
MHDA- 2014/06/24 06:00
PMCR- 2013/10/20
CRDT- 2013/10/22 06:00
PHST- 2013/07/26 00:00 [received]
PHST- 2013/10/15 00:00 [accepted]
PHST- 2013/10/22 06:00 [entrez]
PHST- 2013/10/22 06:00 [pubmed]
PHST- 2014/06/24 06:00 [medline]
PHST- 2013/10/20 00:00 [pmc-release]
AID - 1471-2407-13-485 [pii]
AID - 10.1186/1471-2407-13-485 [doi]
PST - epublish
SO  - BMC Cancer. 2013 Oct 20;13:485. doi: 10.1186/1471-2407-13-485.