Bone Invasion by Walker 256 Carcinoma, Line A in Young and Adult Rats: Effects of Etidronate

Abstract

Line A of Walker 256 carcinoma implanted in the muscle adjacent to the tibia of young (6 weeks) and adult (9 months) male rats invaded the bone. Osteolysis and reactive growth were greater in the bone of young animals than in adults. Ethane-1-hydroxy-1,1-bisphosphonate prevented bone lysis and tumor invasion of the cortex both in young and adult animals. This model may be useful for studies of age-related differences in tumor infiltration into the bone and for investigating drug effects on this process.

Pharmacologic inhibitors of IκB kinase suppress growth and migration of mammary carcinosarcoma cellsin vitroand prevent osteolytic bone metastasisin vivo

“…In this regard, previous studies with bisphosphonates have shown that both nitrogen and nonnitrogen-containing bisphosphonates are also effective at inhibiting osteolytic lesions in the Swiss Walker 256 model, whereas these agents have not been shown to have a systemic antitumor effect (39)(40)(41)(42). In view of the fact that IKK inhibitors have a direct inhibitory effect on tumor growth in some tumor models, it would be of great interest in future studies to directly compare the effects of IKK inhibitors and bisphosphonates on the development of osteolytic lesions and systemic tumor growth in this model.…”

A quantitative model for spontaneous bone metastasis: evidence for a mitogenic effect of bone on Walker 256 cancer cells

“…This model analyses the spontaneous hematogenous metastasis of intramuscularlyinjected W256 tumor cells to bone and other organs, with detailed histomorphometry of bone and comparison of primary and metastatic tumor cell growth rate. The W256 carcinosarcoma has been well established as a tumor model which consistently invades [16,17] and metastasizes to bone [18,20], where it causes significant osteopenia [9,10,17,18] and often hypercalcemia [9,18,19]. This study is the first to describe the spontaneous hematogenous spread of W256 cells from a solid primary tumor over time, and which provides detailed, quantified histologic analysis of distant metastatic target organs, including bone and soft tissues.…”

“…This study is the first to describe the spontaneous hematogenous spread of W256 cells from a solid primary tumor over time, and which provides detailed, quantified histologic analysis of distant metastatic target organs, including bone and soft tissues. The model represents a significant advance for the study of bone metastasis compared to other in vivo models which involve the invasion of bone from contiguous intramuscular tumors [15,16], the intraosseous injection of W256 cells [17], or non-spontaneous metastasis via intraarterial injection [10,15,[18][19][20]. Furthermore, several W256 models have employed non-quantitative [15,17] and/or non-histologic methods [9,16,18] such as X-ray analysis [15][16][17][18] in the attempt to detect osteolysis or bone metastasis.…”

“…This model has permitted us to establish the pattern of spread of tumor cells, their growth rates in primary and metastatic sites, and their effects on the structure and metabolism of bone. We argue that this model is more relevant to mechanisms of bone metastasis than other in vivo models which involve direct invasion of bone from contiguous intramuscular tumor [15,16], intraosseous injection of W256 cells [17] or non-spontaneous metastasis via intra-arterial injection [10,15,[18][19][20]. This is the first detailed study to describe the spontaneous hematogenous spread of W256 cells from a solid primary tumor over time, and provides quantified histologic analysis of distant metastatic target organs, including bone and soft tissues.…”

Bisphosphonates in the Treatment of Glucocorticoid-Induced Osteoporosis

“…They also inhibit bone resorption mediated by tumor products in vitro [17] and in vivo [18][19][20]. The activity of the different bisphosphonates on bone resorption varies markedly.…”