PMID- 20585037
OWN - NLM
STAT- MEDLINE
DCOM- 20100908
LR  - 20181201
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 185
IP  - 3
DP  - 2010 Aug 1
TI  - Role of the CXCR4/CXCL12 axis in lymphangioleiomyomatosis and angiomyolipoma.
PG  - 1812-21
LID - 10.4049/jimmunol.0902149 [doi]
AB  - Lymphangioleiomyomatosis (LAM) is a progressive disease caused by accumulation of 
      metastatic (LAM) cells in the lungs, lymphatics, and the tumor angiomyolipoma 
      (AML). LAM cells have biallelic loss of either tuberous sclerosis complex gene 
      (but predominantly TSC-2) and resultant dysregulation of the mammalian target of 
      rapamycin (mTOR) pathway. Chemokines are associated with neoplastic cell growth, 
      survival, and homing to specific organs and may play similar roles in LAM. Our 
      objective was to study comprehensively the expression and function of chemokine 
      receptors and how their function interacts with dysregulation of the mTOR pathway 
      in LAM and AML. We used RT-PCR and FACS to study receptor expression in primary 
      AML cells and immunohistochemistry to investigate expression in tissues. 
      Chemokine receptor function was analyzed in AML cells by Western blotting of 
      signaling proteins and cell proliferation and apoptosis assays. Primary AML 
      cells, LAM, and AML tissues expressed CCR3, CXCR4, CXCR6, and CXC3CR1. In AML 
      cells, their ligands CXCL12 CX3CL1, CCL11, CCL24, and CCL28 caused robust 
      phosphorylation of p42/44 MAPK and Akt. CXCL12 was expressed in type II 
      pneumocytes covering LAM nodules and caused AML cell growth and protection from 
      apoptosis, which was blocked by AMD3100, a CXCR4 inhibitor. The mTOR inhibitor 
      rapamycin, but not AMD3100, inhibited growth of AML tumor xenografts. We conclude 
      that the CXCL12/CXCR4 axis promotes, but is not absolutely required for, AML/LAM 
      cell growth and survival.
FAU - Clements, Debbie
AU  - Clements D
AD  - Division of Therapeutics and Molecular Medicine and National Institute for Health 
      Research Respiratory Biomedical Research Unit, University of Nottingham, 
      University Hospital, Queens Medical Centre, Nottingham, United Kingdom. 
      debbie.clements@nottingham.ac.uk
FAU - Markwick, Lee J
AU  - Markwick LJ
FAU - Puri, Nidhi
AU  - Puri N
FAU - Johnson, Simon R
AU  - Johnson SR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100628
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (CXCL12 protein, human)
RN  - 0 (CXCR4 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (Tuberous Sclerosis Complex 1 Protein)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - Angiomyolipoma/*immunology/metabolism/*pathology
MH  - Animals
MH  - Apoptosis Regulatory Proteins/biosynthesis/metabolism/physiology
MH  - Cell Line, Transformed
MH  - Cell Movement/immunology
MH  - Cell Proliferation
MH  - Cell Survival/immunology
MH  - Chemokine CXCL12/biosynthesis/metabolism/*physiology
MH  - Female
MH  - Humans
MH  - Inflammation Mediators/physiology
MH  - Lung Neoplasms/immunology/metabolism/pathology
MH  - Lymphangioleiomyomatosis/*immunology/metabolism/*pathology
MH  - Mice
MH  - Mice, Nude
MH  - Receptors, CXCR4/biosynthesis/metabolism/*physiology
MH  - Signal Transduction/immunology
MH  - Tuberous Sclerosis Complex 1 Protein
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Proteins/physiology
MH  - Xenograft Model Antitumor Assays
EDAT- 2010/06/30 06:00
MHDA- 2010/09/09 06:00
CRDT- 2010/06/30 06:00
PHST- 2010/06/30 06:00 [entrez]
PHST- 2010/06/30 06:00 [pubmed]
PHST- 2010/09/09 06:00 [medline]
AID - jimmunol.0902149 [pii]
AID - 10.4049/jimmunol.0902149 [doi]
PST - ppublish
SO  - J Immunol. 2010 Aug 1;185(3):1812-21. doi: 10.4049/jimmunol.0902149. Epub 2010 
      Jun 28.