ABSTRACT
A 7-year-old neutered female Boerboel cross was examined for progressive left pelvic limb lameness. There was no left patellar reflex but the remaining pelvic limb reflexes were hyperreflexic. Radiographically, there was a poorly mineralized opacity occupying the intervertebral foramen at LA-L5. On computed tomography images there was a hyperattenuating intramedullary lesion at LA-L5 that continued caudally, lateralized to the left and became extramedullary, terminating at L5-L6. In addition, well marginated, hyperattenuating lesions were noted at two muscular sites. The dog underwent euthanasia and a caudal esophageal mass was found at post mortem examination. The tumors in the spinal cord, the esophagus, and the skeletal muscles were diagnosed histologically as low-grade chondrosarcoma undergoing endochondral ossification. Spirocerca lupi-induced esophageal chondrosarcoma was believed to be the primary site from which the other, presumably metastatic, lesions originated.
Subject(s)
Chondrosarcoma/veterinary , Dog Diseases/diagnosis , Esophageal Neoplasms/veterinary , Spinal Cord Neoplasms/veterinary , Spirurida Infections/veterinary , Thelazioidea , Animals , Chondrosarcoma/diagnosis , Chondrosarcoma/parasitology , Chondrosarcoma/secondary , Dog Diseases/parasitology , Dogs , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/parasitology , Esophageal Neoplasms/pathology , Euthanasia, Animal , Female , Spinal Cord Neoplasms/diagnosis , Spinal Cord Neoplasms/parasitology , Spinal Cord Neoplasms/secondary , Spirurida Infections/complications , Thelazioidea/isolation & purification , Tomography, X-Ray Computed/veterinaryABSTRACT
Connective tissue growth factor (CTGF/CCN2) plays a critical role in endochondral bone formation; however, CCN2 also promotes angiogenesis and bone metastasis in breast cancer. Chondrocytic HCS-2/8 cells and breast cancer MDA231 cells produce over 6 times more CCN2 than any other cell type. In this study, we demonstrate that these cell lines employ different transcriptional strategies for ccn2 gene induction. Four tandem copies of the dominant transcriptional enhancer in chondrocytes (4 x TRENDIC) were chimerically connected to an SV40 promoter-luciferase construct and subsequently analyzed. The enhancement of the promoter activity by 4 x TRENDIC was greater in the HCS-2/8 cells (7-fold) than in the other 4 cell lines (3-4 fold). The TRENDIC-binding protein complex was detected at a higher signal in the HCS-2/8 cells than in the other cell lines. In addition, the HCS-2/8 nuclear factors strongly targeted not only TRENDIC, but also the previously reported basal control element and a novel enhancer element in the ccn2 promoter. In contrast, high-level ccn2 gene induction in MDA231 cells was largely dependent on Smad signaling through the Smad-binding element in the ccn2 promoter. Based on these results, we propose a model of differential transcription of the ccn2 gene between the chondrocytic cell line and the breast cancer cell line, and therefore imply that these cells utilize distinct transcriptional strategies to obtain the enhanced CCN2 production that is not observed in other types of cells.