CXCL12 alone is insufficient for gliomagenesis in Nf1 mutant mice.
Tumorigenesis requires interactions between tumor progenitors and their microenvironment. We found that low cAMP levels were sufficient for tumorigenesis in a mouse model of Neurofibromatosis-1 (NF1)-associated optic pathway glioma (OPG). We hypothesized that the distinct pattern of glioma in NF1 reflected spatiotemporal differences in CXCL12 effects on cAMP levels. Thus, we sought to alter the pattern of gliomagenesis through manipulation of CXCL12-CXCR4 pathway activation in Nf1 OPG mice. Forced CXCL12 expression induced glioma at a low frequency. Further, treatment of Nf1 OPG mice with AMD3100, a CXCR4 antagonist, did not attenuate glioma growth. Thus, it appears, CXCL12 alone cannot promote gliomagenesis in NF1 mice.
Sun
Tao
T
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Gianino
Scott M
SM
Jackson
Erin
E
Piwnica-Worms
David
D
Gutmann
David H
DH
Rubin
Joshua B
JB
D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D051379:Mice; D008818:Mice, Neurologic Mutants; D025542:Neurofibromin 1 / Q000235:genetics / Q000502:physiology*; D020339:Optic Nerve Glioma / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology
D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D025542:Neurofibromin 1