Rapid growth of cutaneous metastases after surgical resection of thrombospondin-secreting small blue round cell tumor of childhood.
In animal models, the importance of tumor-derived antiangiogenic factors in controlling metastases has been demonstrated by the growth acceleration of distant metastases after surgical excision of a primary tumor mass. We report the case of an infant who developed rapidly growing cutaneous metastases after surgical resection of a neoplasm of an upper extremity. The tumor was undifferentiated, with some morphological features of primitive neuroectodermal tumor. To test the possibility that the primary tumor was secreting an angiogenic inhibitor, cells from the primary tumor were grown in culture, and the culture medium was tested with an in vitro endothelial cell migration assay and Western blot. The cultured cells secreted sufficiently high levels of an angiogenic inhibitor to overcome the inducing ability of vascular endothelial growth factor and basic fibroblast growth factor. One of the secreted proteins was thrombospondin-1, a potent antiangiogenic glycoprotein. The rapid dissemination of distant metastases after resection of the primary tumor in this case suggests that tumor-derived angiogenic inhibitors are important in maintaining the local net balance of angiogenic mediators controlling the growth of micrometastasis.
Department of Pathology, Children's Memorial Hospital, Northwestern University Medical School, Chicago, IL 60614, USA.
S E
SE
Crawford
E M
EM
Flores-Stadler
L
L
Huang
X D
XD
Tan
M
M
Ranalli
Y
Y
Mu
F
F
Gonzalez-Crussi
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D018302:Neoplasms, Neuroepithelial / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000378:metabolism / Q000473:pathology*; D012509:Sarcoma / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000473:pathology / Q000556:secondary* / Q000601:surgery; D019699:Thrombospondins / Q000378:metabolism*
D019699:Thrombospondins