PubMed · 1922411
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T L Pope. 1991. Comment on Ewing's sarcoma article.. https://pubmed.ncbi.nlm.nih.gov/1922411/
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Transforming growth factor (TGF)-beta promotes breast cancer metastasis to bone. To determine whether the osteolytic factor parathyroid hormone-related protein (PTHrP) is the primary mediator of the tumor response to TGF-beta, mice were inoculated with MDA-MB-231 breast cancer cells expressing a constitutively active TGF-beta type I receptor. Treatment of the mice with a PTHrP-neutralizing antibody greatly decreased osteolytic bone metastases. There were fewer osteoclasts and significantly decreased tumor area in the antibody-treated mice. TGF-beta can signal through both Smad and mitogen-activated protein (MAP) kinase pathways. Stable transfection of wild-type Smad2, Smad3, or Smad4 increased TGF-beta-stimulated PTHrP secretion, whereas dominant-negative Smad2, Smad3, or Smad4 only partially reduced TGF-beta-stimulated PTHrP secretion. When the cells were treated with a variety of protein kinases inhibitors, only specific inhibitors of the p38 MAP kinase pathway significantly reduced both basal and TGF-beta-stimulated PTHrP production. The combination of Smad dominant-negative blockade and p38 MAP kinase inhibition resulted in complete inhibition of TGF-beta-stimulated PTHrP production. Furthermore, TGF-beta treatment of MDA-MB-231 cells resulted in a rapid phosphorylation of p38 MAP kinase. Thus, the p38 MAP kinase pathway appears to be a major component of Smad-independent signaling by TGF-beta and may provide a new molecular target for anti-osteolytic therapy.
STUDY DESIGN: A case report is presented. OBJECTIVE: To present a previously unreported complication of procuring anterior iliac crest autograft. SUMMARY OF BACKGROUND DATA: Many complications that involve the common procedure of procuring iliac crest autograft have been reported and studied. The incidental finding of a neoplasm in an iliac crest autograft in an otherwise asymptomatic patient has not been reported previously. METHODS: A case of benign fibrous histiocytoma is presented as it was found incidentally during the procurement of the anterior iliac crest for anterior cervical fusion. Intraoperative decision making and alternatives for this challenging situation are reviewed. RESULTS: An iliac crest bone graft with a grossly unusual appearance was noted at the time of autograft procurement. The autograft was aborted, and an iliac crest allograft was substituted for the autograft to complete the planned cervical fusion. The lesion was later identified histopathologically and clinically as a benign fibrous histiocytoma. Postoperative computed tomography demonstrated the extent of the lesion. CONCLUSIONS: The intraoperative finding of a bony neoplasm at a planned autograft donor site in an otherwise healthy patient supports routine preoperative discussion of allograft alternatives. All patients undergoing surgery in which autograft is to be used should be informed regarding the possibility of allograft substitution. When a neoplasm is encountered unexpectedly, oncologic principles of obtaining frozen section or a touch-prep for diagnosis, avoiding the use of suspect graft material as well as cross-contamination of iliac crest and anterior cervical surgical sites, should be applied. Care should be taken intraoperatively with potentially contaminated drapes and instruments.
BACKGROUND: Progressive prostate cancer typically metastasizes to bone where prostate cancer cells gain an osteoblast-like phenotype and induce osteoblastic metastases through unknown mechanisms. To investigate the biology of prostate cancer skeletal metastases, we compared gene expression between the non-metastatic LNCaP cell line and its derivative cell line C4-2B that metastasizes to bone. METHODS: Total RNA from LNCaP and C4-2B cell lines was isolated and used to probe membrane-based gene arrays (Comparison 1). Additionally, LNCaP cells were incubated in the absence or presence of conditioned media (CM) from a human osteoblast-like cell line (HOBIT) and total RNA from these cells was used to probe gene arrays (Comparison 2). Differential expression of genes was confirmed by RT-PCR. RESULTS: Of the 1,176 genes screened, 35 were differentially expressed between LNCaP and C4-2B cells (Comparison 1). HOBIT-CM induced differential expression of 30 genes in LNCaP cells (Comparison 2). Interestingly, 19 genes that were differentially expressed in C4-2B vs. LNCaP also displayed a similar expression pattern in LNCaPs grown in HOBIT-CM. These genes are primarily involved in motility, metabolism, signal transduction, tumorigenesis, and apoptosis. CONCLUSIONS: These results suggest that osteoblasts produce soluble factors that contribute to the progression of prostate cancer skeletal metastases, including their transition to an osteoblast-like phenotype. Additionally, these data provide targets to explore for further investigations towards defining the biology of skeletal metastases.