The tumor microenvironment: CXCR4 is associated with distinct protein expression patterns in neuroblastoma cells.
In previous studies, we demonstrated that human neuroblastoma cells are equipped with the machinery to direct their homing to bone marrow. These tumor cells express the CXCR4 receptor for the bone marrow stroma-derived chemokine CXCL12 (SDF-1) and secrete the CXCL12 ligand. The present study was undertaken to explore possible differences in gene-expression patterns between neuroblastoma variants that over-express CXCR4 (designated STH cells) and those which express very little of this receptor (STL cells). The results of the study clearly indicate that these variants show a differential gene-expression profile. They differ in expression of some integrins such as VLA2, VLA3 and VLA6, of neuroendocrine-markers such as CD56 and synaptophysin, in the expression of c-kit and in the secretion of certain cytokines and growth factors such as TNFalpha, SDF-1, VEGF, IL-8, GM-CSF and IP-10. We hypothesize that these differences are due to an autocrine SDF-1alpha-CXCR4 axis.
Nevo
Ido
I
Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.
Sagi-Assif
Orit
O
Meshel
Tsipi
T
Geminder
Hila
H
Goldberg-Bittman
Lilach
L
Ben-Menachem
Shlomit
S
Shalmon
Bruria
B
Goldberg
Iris
I
Ben-Baruch
Adit
A
Witz
Isaac P
IP
D019002:CD56 Antigen / Q000276:immunology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000378:metabolism; D009447:Neuroblastoma / Q000276:immunology*; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000276:immunology*; D016708:Synaptophysin / Q000276:immunology / Q000378:metabolism
D019002:CD56 Antigen; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D016207:Cytokines; D016023:Integrins; D019718:Receptors, CXCR4; D016708:Synaptophysin; D019009:Proto-Oncogene Proteins c-kit