glycogen and Chordoma

Chordoma is a rare tumor of the bone derived from remnants of the notochord with pronounced chemoresistance. A common feature of the notochord and chordoma cells is distinct vacuolization. Recently, the notochord vacuole was described as a lysosome-related organelle. Since lysosomes are considered as mediators of drug resistance in cancer, we were interested whether they may also play a role in chemoresistance of chordoma. We characterized the lysosomal compartment in chordoma cell lines by cytochemistry, electron microscopy (ELMI) and mutational analysis of genes essential for the physiology of lysosomes. Furthermore, we tested for the first time the cytotoxicity of chloroquine, which targets lysosomes, on chordoma. Cytochemical stainings clearly demonstrated a huge mass of lysosomes in chordoma cell lines with perinuclear accumulation. Also vacuoles in chordoma cells were positive for the lysosomal marker LAMP1 but showed no acidic pH. Genetic analysis detected no apparent mutation associated with known lysosomal pathologies suggesting that vacuolization and the huge lysosomal mass of chordoma cell lines is rather a relict of the notochord than a result of transformation. ELMI investigation of chordoma cells confirmed the presence of large vacuoles, lysosomes and autophagosomes with heterogeneous ultrastructure embedded in glycogen. Interestingly, chordoma cells seem to mobilize cellular glycogen stores via autophagy. Our first preclinical data suggested no therapeutically benefit of chloroquine for chordoma. Even though, chordoma cells are crammed with lysosomes which are according to their discoverer de Duve "cellular suicide bags". Destabilizing these "suicide bags" might be a promising strategy for the treatment of chordoma.

Topics: Antineoplastic Agents; Autophagy; Bone Neoplasms; Cell Proliferation; Cell Survival; Chloroquine; Chordoma; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Glycogen; Humans; Lysosomes; Tumor Cells, Cultured

A morphologic and electron microscopic study was made of two chordoid sarcomas. These lesions were compared with two classical chondrosarcomas and two chordomas. These chondrosarcoma cells showed many features common to chondrocytes, such as abundant RER, well-developed Golgi complexes, and microvillous cytoplasmatic membranes. The chordoid sarcomas bore a close morphologic resemblance to the chordomas but the ultrastructural features revealed a close relationship to the chondrosarcomas. The chordoid sarcoma and chondrosarcoma cells had scalloped cytoplasmatic membranes, variable amounts of glycogen, round or oval nuclei and microfibrils, collagen, and electron-dense granules in the ground substance. The chordoma was characterized by the presence of stellate and physalipherous cells, as well as many transitional cells, with varying nuclear morphology; dilated and irregular RER in contact with mitochondria and morphologically varied vacuoles are the main features in the cytoplasm. This study suggests that chordoid sarcoma represents a variety of the chondrosarcoma rather than a form of chordoma. These findings also support the suggestion of Weiss that chordoid sarcoma is an extraskeletal myxoid chondrosarcoma.

Topics: Cell Nucleus; Chondrosarcoma; Chordoma; Collagen; Cytoplasmic Granules; Cytoskeleton; Endoplasmic Reticulum; Glycogen; Golgi Apparatus; Humans; Intracellular Membranes; Microscopy, Electron; Vacuoles

The electron microscopic study of a sacral chordoma, the cells of which contain variable amounts of glycogen, allowed to characterize different stages in the evolution of the tumoral cells. The young cells contain almost no glycogen ; progressively it becomes more abundant and fills up almost the whole cytoplasm. At the end of the evolution glycogen disappears while the cell becomes vacuolated. This suggests that enzymatic lysis of this polysaccharide could be the cause of the vacuolation which finally produces the physaliferous cell. Comparison between the cells of the chordoma and those of the normal notochord shows some morphological similarities in the development of these cells. These different data may be useful for a classification of the various types of chordomas.

Topics: Adult; Cell Nucleolus; Cell Nucleus; Chordoma; Chromatin; Cytoplasm; Glycogen; Humans; Male; Sacrum; Spinal Neoplasms; Vacuoles

Cytologic and cytochemical examination of eighteen cases of round-cell sarcoma of bone allowed classification of these tumors into four cytologic groups. Additional cytochemical examinations based on the PAS and D-PAS reactions, and the demonstration of the activity of peroxidase, naphtol-ASD-Chloracetate esterase, alpha-naphthylacetate esterase, naphthol-AS-acetate esterase with and without sodium fluoride inhibition, acid and alkaline phosphatases yielded no evidence of uniform behavior among the individual groups or within any single group. The studies showed that a positive glycogen reaction cannot be used as a basic criterion for the classification of such tumors as Ewing's sarcoma and for regarding them as a uniform tumor group. It is possible that a pool of tumors is involved, including tumors of monocytic and probably of lymphocytic origin, reticulum-cell sarcoma, tumors of myelocytic and erythroplastic origin, stem-cell tumors, and endothelial-cell tumors. Histologic examination alone is not sufficient for the classification of round-cell sarcomas of bone, and it should be supplemented by cytologic and cytochemical or histochemical methods. Osteosarcomas (23 cases) and chondrosarcomas (8 cases) display cells which are characteristic for these tumors and which could be correlated with their benign counterparts, osteoblasts and chondroid cells. The histologically recognizable degree of malignancy of chondrosarcoma can be evaluated better with the cytologic than with the histologic technic. Indications of the possibilities of differential diagnosis based on the cytologic pictures of benign and malignant osteoplastic and chondroplastic tumors, giant-cell tumors and chordoma are discussed.

Topics: Adolescent; Bone Neoplasms; Cell Nucleolus; Cell Nucleus; Child; Chondroblastoma; Chondroma; Chondrosarcoma; Chordoma; Cytoplasm; Female; Giant Cell Tumors; Glycogen; Humans; Infant; Male; Naphthol AS D Esterase; Osteosarcoma; Periodic Acid-Schiff Reaction; Phosphoric Monoester Hydrolases; Sarcoma; Sarcoma, Ewing

The ecchordosis physaliphora, a small gelatinous mass attached to the midline of the clivus, is characterized ultrastructurally by glycogen-laden intracytoplasmic vacuoles, focally distended endoplasmic reticulum and perinuclear cisterns with cytoplasmic invaginations, large clusters of granular endoplasmic reticulum interdigitating with mitochondria, and an abundant extracellular space. These morphologic features are also present in the 9-day embryonal chick notochord and the human chordoma and serve to reaffirm the derivation of the ecchordosis and chordoma from notochordal rests.

Topics: Animals; Chick Embryo; Chordoma; Embryo, Mammalian; Endoplasmic Reticulum; Extracellular Space; Glycogen; Humans; Microscopy, Electron; Mitochondria

Topics: Adipose Tissue; Cartilage; Chondrosarcoma; Chordoma; Connective Tissue; Female; Fibroma; Fibrosarcoma; Glycogen; Hemangioma; Humans; Leiomyoma; Leiomyosarcoma; Lipoma; Liposarcoma; Muscle, Smooth; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Neoplasms, Nerve Tissue; Neurilemmoma; Neurofibroma; Sarcoma; Sarcoma, Synovial; Synovial Membrane; Uterus

Topics: Aged; Chordoma; Female; Glycogen; Glycosaminoglycans; Histocytochemistry; Humans; Lung Neoplasms; Neoplasm Metastasis; Rectal Neoplasms; Sacrum; Spinal Neoplasms

Topics: Cell Differentiation; Chordoma; Endoplasmic Reticulum; Glycogen; Humans; Microscopy, Electron; Mitochondria; Sacrococcygeal Region