A spontaneous subcutaneous tumor in C57BL/6 mice that metastasizes to the liver.
A malignant tumor that arose spontaneously in the subcutaneous tissue of the back of a C57BL/6 female mouse was found to metastasize spontaneously to the liver. The primary and metastatic tumors, SML (spontaneous metastasis to the liver) 1 and SML 2, were established in vitro in long-term cell suspension culture and were passaged 10 times in vivo for 18 months. When 100,000 cells were injected subcutaneously in the orthotopic position, tumor growth appeared in 60% of the SML 1 mice and 100% of the SML 2 mice. SML 1 did not grow when injected in the footpad, while SML 2 did. The median survival was 47 days for SML 1 and 48.5 days for SML 2 (P = 0.013). The pattern of metastasis was similar for both tumor cell lines, irrespective of intravenous or subcutaneous injection routes. Spontaneous metastasis of the SML 2 line occurred from both the orthotopic and heterotopic sites, while the SML 1 metastasized spontaneously from the orthotopic site only. Liver metastasis appeared in > 90% of the mice for both SML 1 and SML 2. Metastasis to the spleen occurred in about half the mice. Other sites of metastasis were the ovaries (36% and 52%, respectively, for SML 1 and SML 2), the kidneys (approximately 15%) and the small bowel (very rarely). Metastasis to the lungs did not occur except very rarely in the later passages of the SML 2 line. Histologic, immunohistochemical and electron microscopic studies showed a histiocytic tumor with macrophage characteristics. The cells exhibited chemotaxis toward liver extracellular matrix and reduced motility toward collagen IV, laminin and fibronectin compared to the B16-F10 melanoma line. This spontaneously occurring tumor should prove useful for the study of organ-specific metastasis to the liver.
Nathanson
S D
SD
Department of Surgery, Henry Ford Hospital, Detroit, MI 48202.
Nelson
L T
LT
Lee
M
M
D000818:Animals; D002455:Cell Division; D002465:Cell Movement; D015925:Cryopreservation; D005260:Female; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000556:secondary / Q000662:veterinary*; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009368:Neoplasm Transplantation; D009928:Organ Specificity; D012376:Rodent Diseases / Q000473:pathology*; D012878:Skin Neoplasms / Q000473:pathology / Q000662:veterinary*; D014407:Tumor Cells, Cultured