Abstract
A reproducible tumor model for bone marrow metastasis has been developed by an injection of murine C-1300 neuroblastoma (C-1300 NB) cells into the tail vein of syngeneic A/J mice. The animals died with liver metastases at 18–21 days after an injection of 105 tumor cells and often had bone marrow metastasis in the femur. N-methylformamide (NMF), a maturational agent, was administered to inhibit liver metastases and to extend survival in mice with advancing bone metastasis. Histological examination of bone marrow metastasis, demonstrated lesions varying from a few small colonies of C-1300 NB cells either in metaphysis or diaphysis to large foci replacing normal hematopoietic bone marrow, simultaneously invading epiphysis or cortex of bone as bone metastasis. This assay demonstrated the ability to detect neuroblastoma cells in the bone marrow histologically and could determine bone marrow TD50 by extraction of bone marrow cells after treatment with various doses of drug. Fifty per cent of mice injected with cyclophosphamide (CY) developed bone marrow metastasis without liver metastasis. Treatment with tamoxifen, an anti-calmodulin drug, suppressed tumor takes in the recipient mice with tamoxifen-dose-dependent fashion. This experimental system allows for investigations into the therapeutic response and biology of neuroblastoma metastases in the bone marrow.
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Young JL, Ries LG, Silverberg E, Horm JW and Miller RW, 1986, Cancer incidence, survival, and mortality for children younger than age 15 years.Cancer,58 (Suppl 2), 598–602.
Evans AE, D'Angio GI and Sather HN, 1990, A comparison of four staging systems for localized and regional neuroblastoma.J Clin Oncol,8, 678–88.
D'Angio GI and Evans AE, 1983, Cyclic, low-dose total body irradiation for metastatic neuroblastoma.Int J Radiat Oncol Biol Phys,9, 1961–5.
Sawaguchi S, Kaneko M, Uchino J,et al. 1990, Treatment of advanced neuroblastoma with emphasis on intensive induction chemotherapy.Cancer,66, 1879–87.
Stackpole CW, Alterman AL and Fornabaio DM, 1985, Growth characteristics of clonal cell populations constituting a B16 melanoma metastasis model system.Invasion Metastasis,5, 125–43.
Fidler IJ and Poste G, 1985, The cellular heterogeneity of malignant neoplasms: implications for adjuvant chemotherapy.Semin Oncol,12, 207–21.
Nicolson GL, 1987, Tumor cell instability, diversification, and progression to the metastatic phenotype: from oncogenes to oncofetal expression.Cancer Res,47, 1473–87.
Kopper L, Yan Hahn TJ and Lapis K, 1982, Experimental model for liver metastasis formation using Lewis lung tumor.J Cancer Res Clin Oncol,103, 31–8.
Lafreniere R and Rosenberg SA, 1986, A novel approach to the generation and identification of experimental hepatic metastases in a murine model.J Natl Cancer Inst,76, 309–22.
Giavazzi R, Jessup JM, Campbell DE, Walder SM and Fidler IJ, 1986, Experimental nude mouse model of human colorectal cancer liver metastases.J Natl Cancer Inst,77, 1303–8.
Bresalier RS, Hujanen ES, Raper SE,et al. 1987, An animal model for colon cancer metastasis; establishment and characterization of murine cell lines with enhanced liver metastatizing ability.Cancer Res,47, 1398–406.
Koike A, Nakazato H and Moore GE, 1963, The fate of Ehrlich cells infected into the portal system.Cancer,16, 716–20.
Goldrosen MH, 1980, Murine colon adenocarcinoma: immunobiology of metastases.Cancer,45, 1223–8.
Arguello F, Baggs RB and Frantz CN, 1988, A murine model of experimental metastasis to bone and bone marrow.Cancer Res,48, 6876–81.
Ingall JRF, 1964, A model for the study of experimental bone metastasis.Proc Soc Exp Biol Med,117, 819–22.
Berrettoni BA and Carter JR, 1986, Mechanisms of cancer metastasis to bone.J Bone Joint Surg,68, 308–12.
Spremulli EN and Pexter DL, 1984, Polar solvents: a novel class of antineoplastic agents.J Clin Oncol,2, 227–40.
Iwakawa M, Tofilon PJ, Arundel C and Milas L, 1989, Combination of N-methylformamide withcis-diaminedichloroplatinum (II) in murine mammary carcinoma: importance of timing.Cancer Res,49, 1640–3.
Kikuchi Y, Iwao I, Sasa Het al. 1990, Restrictive effects of calmodulin antagonists on reduced cisplatin uptake by cisplatin-resistant human ovarian cancer cells.Gynecol Oncol 39, 199–203.
Hait WH and Lazo S, 1986, Calmodulin: a potential target for cancer chemotherapeutic agents.J Clin Oncol 4, 994–1012.
Iwakawa M, 1992, High content of calcium and calmodulin in human neuroblastoma tumor cells.Proceedings of the Japanese Cancer Association 51st Annual Meeting,1164, p. 213.
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Iwakawa, M., Ando, K., Ohkawa, H. et al. A murine model for bone marrow metastasis established by an i.v. injection of C-1300 neuroblastoma in A/J mice. Clin Exp Metast 12, 231–237 (1994). https://doi.org/10.1007/BF01753891
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DOI: https://doi.org/10.1007/BF01753891