A subcutaneous mass in the right femoral region of a female F344 Slc/N rat was examined histopathologically. At 83 weeks of age, the animal showed symptoms of severe anemia and nasal bleeding. Necropsy revealed that the mass had invaded the skeletal muscles but did not affect the bones. Multicentric nodules were also observed in the lung. Histopathology revealed a sheet-like growth pattern of polygonal tumor cells with round or comma-shaped nuclei and pale eosinophilic cytoplasm. Osteoid tissue was observed in not only the original lesion but also the metastatic foci in the lung. Each tumor cell was surrounded by argentophil fibers and few collagen fibers. Immunohistochemically, the tumor cells were positive for proliferating cell nuclear antigen (PCNA), vimentin, osterix and osteocalcin, but negative for keratin, S-100, von Willebrand factor, CD-31, CD-34, desmin, α-smooth muscle actin, lysozyme, α1-antitrypsin and rat malignant fibrous histiocytoma (MFH) antigen. CD-68-positive cells were considered to be infiltrated macrophages because they were negative for PCNA. On the basis of these findings, we diagnosed the present case as extraskeletal osteosarcoma.

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Abstract. Gicerin, an Ig-superfamily cell adhesion molecule, appears transiently in embryonic tissues including those of the nervous, urogenital, respiratory and digestive systems, and it promotes neurite extension, cell migration and epithelialization through its cell adhesive activities. In addition, gicerin also reappears in regenerating tissue after suffering either a traumatic injury or a viral infection. In the present study, we examined the expression pattern of gicerin in the regeneration of hepatocytes. Immunohistochemically, gicerin protein appeared in the regenerating hepatocytes of carbon tetrachloride (CCl 4 )-induced acute hepatitis, while it was scarcely expressed in the hepatocytes of normal mouse liver. Real-time PCR revealed the up-regulation of gicerin transcription in the regenerating process of CCl 4 -induced hepatitis. The expression of transforming growth factor (TGF)-ß1 was also increased during the regeneration. Furthermore, the gicerin mRNA expression increased during the process of an in vitro hepatocyte regeneration model using mouse primary hepatocytes and hepa 1-6 cells. To note, the mRNA levels of gicerin in these cells were enhanced by the presence of TGF-ß1. Collectively, these findings suggest that TGF-ß1 may therefore regulate gicerin expression in hepatocytes leading to liver regeneration by cell-cell or cell-ECM interactions.

Gicerin is a cell adhesion molecule in the immunoglobulin (Ig) superfamily and plays an important role during development through its adhesive properties. Gicerin has two isoforms that differ in their cytoplasmic domains; s-gicerin is the shorter and l-gicerin the longer form of the protein. Gicerin is over-expressed in some sporadic tumors as well as in developing tissues. To provide direct evidence that gicerin has the potential to participate in malignant aspects of tumor cell behavior, a gicerin cDNA was introduced into L-929 cells, an endogenous gicerin-negative mouse fibroblast and subsequently analyzed for changes in their invasive and metastatic potential by implantation into nude mice and chick embryos. Compared with parental cells, both gicerin isoform transfectants showed an enhanced cell growth and invaded deeply into surrounding tissues from implanted sites in both animal models. Furthermore, l-gicerin transfectants markedly enhanced metastasis to the lung. These findings suggest that gicerin promotes the tumor growth and invasion, and the isoform bearing the longer cytoplasmic domain may play a role in metastasis.