Analysis of steroid hormone effects on xenografted human NF1 tumor schwann cells.
The neurofibroma, a common feature of neurofibromatosis type 1 (NF1), is a benign peripheral nerve sheath tumor that contains predominantly Schwann cells (SC). There are reports that neurofibroma growth may be affected by hormonal changes, particularly in puberty and pregnancy, suggesting an influence by steroid hormones. This study examined the effects of estrogen and progesterone on proliferation and apoptosis in a panel of NF1 tumor xenografts. SC-enriched cultures derived from three human NF1 tumor types (dermal neurofibroma, plexiform neurofibroma, and malignant peripheral nerve sheath tumor (MPNST)) were xenografted in sciatic nerves of ovariectomized scid /Nf1-/+ mice. At the same time, mice were implanted with time-release pellets for systemic delivery of progesterone, estrogen or placebo. Proliferation and apoptosis by the xenografted SC were examined two months after implantation, by Ki67 immunolabeling and TUNEL. Estrogen was found to increase the growth of all three MPNST xenografts. Progesterone was associated with increased growth in two of the three MPNSTs, yet decreased growth of the other. Of the four dermal neurofibroma xenografts tested, estrogen caused a statistically significant growth increase in one, and progesterone did in another. Of the four plexiform neurofibroma SC xenografts, estrogen and progesterone significantly decreased growth in one of the xenografts, but not the other three. No relationship of patient age or gender to steroid response was observed. These findings indicate that human NF1 Schwann cells derived from some tumors show increased proliferation or decreased apoptosis in response to particular steroid hormones in a mouse xenograft model. This suggests that anti-estrogen or anti-progesterone therapies may be worth considering for specific NF1 neurofibromas and MPNSTs.
Li
Hua
H
Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA.
Zhang
Xuelian
X
Fishbein
Lauren
L
Kweh
Frederick
F
Campbell-Thompson
Martha
M
Perrin
George Q
GQ
Muir
David
D
Wallace
Margaret
M
D000293:Adolescent; D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004343:Drug Implants; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007223:Infant; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D009456:Neurofibromatosis 1 / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D012583:Schwann Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
D004343:Drug Implants; D004967:Estrogens; D019394:Ki-67 Antigen; D011374:Progesterone