PMID- 22865455
OWN - NLM
STAT- MEDLINE
DCOM- 20121221
LR  - 20211021
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 72
IP  - 19
DP  - 2012 Oct 1
TI  - CD133+ melanoma subpopulations contribute to perivascular niche morphogenesis and 
      tumorigenicity through vasculogenic mimicry.
PG  - 5111-8
LID - 10.1158/0008-5472.CAN-12-0624 [doi]
AB  - Tumor cell subpopulations that express cancer stem cell markers such as CD133 
      (prominin1) or ABCB5 are thought to be crucial for tumor initiation and 
      heterogeneity, but their biological significance in melanoma has been 
      controversial. Here, we report that CD133(+) and ABCB5(+) subpopulations are 
      colocalized in melanomas in perivascular niches that contain CD144 
      (VE-cadherin)(+) melanoma cells forming vessel-like channels, a phenomenon termed 
      vasculogenic mimicry (VM). RNAi-mediated attenuation of CD133 established its 
      critical function in morphogenesis of these perivascular niches as well as in 
      melanoma tumorigenicity. Niche-associated genes CD144 and ABCB5 were 
      downregulated in tumors derived from CD133 knockdown (KD) melanoma cells compared 
      with controls. CD133KD cells also lacked the ability to form CD144(+) VM-like 
      channels in a manner that was associated with a depletion of the ABCB5(+) cell 
      subpopulation. Finally, CD133 KD cells exhibited poorer tumor growth in vivo. 
      Taken together, our findings corroborate models in which CD133(+)/ABCB5(+) 
      melanoma cells reside in a complex anastomosing microvascular niche that 
      encompasses CD144(+) VM channels as well as authentic endothelial cell-lined 
      blood vessels. Further, they indicate that CD133(+) cells act as stem-like cells, 
      which drive tumor growth by promoting VM and the morphogenesis of a specialized 
      perivascular niche in melanoma.
CI  - (c)2012 AACR.
FAU - Lai, Chiou-Yan
AU  - Lai CY
AD  - Program in Dermatopathology, Department of Pathology, Brigham and Women's 
      Hospital, Harvard Medical School, Boston, Massachusetts, USA.
FAU - Schwartz, Brian E
AU  - Schwartz BE
FAU - Hsu, Mei-Yu
AU  - Hsu MY
LA  - eng
GR  - R01 CA138649/CA/NCI NIH HHS/United States
GR  - R01-CA138649/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120803
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (ABCB5 protein, human)
RN  - 0 (AC133 Antigen)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Antigens, CD)
RN  - 0 (Cadherins)
RN  - 0 (Glycoproteins)
RN  - 0 (PROM1 protein, human)
RN  - 0 (Peptides)
RN  - 0 (Prom1 protein, mouse)
RN  - 0 (cadherin 5)
SB  - IM
MH  - AC133 Antigen
MH  - ATP Binding Cassette Transporter, Subfamily B
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics/metabolism
MH  - Animals
MH  - Antigens, CD/*genetics/metabolism
MH  - Blotting, Western
MH  - Cadherins/genetics/metabolism
MH  - Cell Line, Tumor
MH  - Cell Transformation, Neoplastic/*genetics/metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - Glycoproteins/*genetics/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Melanoma/blood supply/*genetics/pathology
MH  - Melanoma, Experimental/blood supply/genetics/pathology
MH  - Mice
MH  - Mice, SCID
MH  - Neoplastic Stem Cells/*metabolism/pathology
MH  - Neovascularization, Pathologic/*genetics/metabolism
MH  - Peptides/*genetics/metabolism
MH  - RNA Interference
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stem Cell Niche/genetics
MH  - Transplantation, Heterologous
MH  - Tumor Burden/genetics
PMC - PMC3463654
MID - NIHMS398523
COIS- Disclosure of Potential Conflict of Interest: No potential conflicts of interest 
      were disclosed.
EDAT- 2012/08/07 06:00
MHDA- 2012/12/22 06:00
PMCR- 2013/10/01
CRDT- 2012/08/07 06:00
PHST- 2012/08/07 06:00 [entrez]
PHST- 2012/08/07 06:00 [pubmed]
PHST- 2012/12/22 06:00 [medline]
PHST- 2013/10/01 00:00 [pmc-release]
AID - 0008-5472.CAN-12-0624 [pii]
AID - 10.1158/0008-5472.CAN-12-0624 [doi]
PST - ppublish
SO  - Cancer Res. 2012 Oct 1;72(19):5111-8. doi: 10.1158/0008-5472.CAN-12-0624. Epub 
      2012 Aug 3.