Murine model for skeletal metastases of Ewing's sarcoma

Abstract

Ewing's sarcoma shows a strong tendency to metastasize to the lungs or the skeleton, or both. A peculiar feature of the secondary involvement of bone with this tumor is that it may also appear in the absence of clinically evident lung metastases, both at clinical presentation and during the course of the disease. Although osseous metastases are critically relevant for prognosis, the pathogenesis of this peculiar feature of Ewing's sarcoma is poorly understood, partly due to the lack of appropriate experimental in vivo models. We show that the intravenous injection of TC-71 Ewing's sarcoma cells into athymic 4-5-week-old Crl/nu/nu (CD1) BR mice reproducibly colonizes specific sites of the skeleton in addition to the lungs and lymph nodes. The distribution and the morphologic appearance of these experimental bone metastases mimic the pattern of skeletal involvement observed in humans. This experimental model of bone metastasis of Ewing's sarcoma may be the basis for future studies aimed at understanding the pathophysiology and treatment of Ewing's sarcoma.

In Ewing's sarcoma CCN3(NOV) inhibits proliferation while promoting migration and invasion of the same cell type

“…In ES, increased migration and invasion is Role of CCN3(NOV) in the biology of Ewing's sarcoma cells S Benini et al associated with reduced cell adhesion to collagen I and IV, which might be due to reduced expression, both at mRNA and protein level, of its main receptor, the integrin a 2 b 1 . ES cells are generally characterized by a high expression of a 5 b 1 , moderate levels of a 6 b 1 , heterogeneous expression of a 2 b 1 and null expression of a 3 b 1 (Scotlandi et al, 2000). Interestingly, in two different ES cell lines, derived from the same patients, a 2 b 1 was higher on primary cells compared with metastatic cells (vanValen et al, 1994).…”

Dysregulation of growth factor signaling in human hepatocellular carcinoma

“…Neutralizing antibodies against IGF-1R such as alpha-IR3 (Jacobs et al, 1986;Arteaga and Osborne, 1989;Kato et al, 1993;Scotlandi et al, 1998) and CP-751,871 (Cohen et al, 2005) diminish receptor autophosphorylation and subsequent signaling owing to receptor internalization and lysosomal degradation (Hailey et al, 2002;Sachdev et al, 2003). dnIGF-1R isoforms with deletions in the cytoplasmic tyrosine kinase domain such as dnIGF-1R 950 and dnIGF-1R 952 Min et al, 2003Min et al, , 2005 and also secreted isoforms like dnIGF-1R 486 and dnIGF-1R 482 (Reiss et al, 1998(Reiss et al, , 2001Min et al, 2003) mediate antineoplastic effects based on the induction of tumor cell apoptosis and growth inhibition.…”

Growth factor receptors as therapeutic targets: strategies to inhibit the insulin-like growth factor I receptor

“…The mouse MAb alpha-IR-3 raised against the alpha domain of IGF-IR inhibited IGF-IR activation and IGF-IR-dependent mitogenicity in several cell types in vitro, including breast carcinoma (Arteaga et al, 1989;Arteaga, 1992), rhabdomyosarcoma (Kalebic et al, 1994), NSCLC (Zia et al, 1996), and Ewing's sarcoma (Scotlandi et al, 1998). However, in some cases alpha-IR-3 was ineffective in blocking IGF-I-sensitive tumors in animal models (Arteaga, 1992).…”