agar and Bone-Neoplasms

Primary bone cancers commonly involve surgery to remove the malignant tumor, complemented with a postoperative treatment to prevent cancer resurgence. Studies on magnetic hyperthermia, used as a single treatment or in synergy with chemo- or radiotherapy, have shown remarkable success in the past few decades. Multifunctional biomaterials with bone healing ability coupled with hyperthermia property could thus be of great interest to repair critical bone defects resulting from tumor resection. For this purpose, we designed superparamagnetic and bioactive nanoparticles (NPs) based on iron oxide cores (γ-Fe

Topics: Agar; Biocompatible Materials; Bone Neoplasms; Glass; Humans; Hyperthermia, Induced; Magnetic Phenomena; Osteosarcoma; Silicon Dioxide

Zinc finger X-chromosomal protein (ZFX) is a member of the zinc finger family of proteins. The importance of ZFX in several cancer types, including prostate cancer, laryngeal squamous cell carcinoma, and glioma, has been addressed. However, the role of ZFX in human osteosarcoma remains unknown. Here we investigated the phenotype of ZFX knockdown on cell proliferation and in vitro tumorigenesis using lentivirus-mediated loss-of-function strategy. The results demonstrated that the proliferation and colony formation ability of human osteosarcoma Saos-2 and MG63 cells was impaired by ZFX small interfering RNA (siRNA)-expressing lentivirus. Moreover, loss of ZFX led to G0/G1 phase cell cycle arrest and a significant increase of cells in the sub-G1 fraction, indicating that ZFX functions as an oncogene in the malignant proliferation process in osteosarcoma. Furthermore, ZFX siRNA may have an antitumorigenic effect on osteosarcoma cells. Our findings hold important significance for RNA interference-mediated cancer gene therapy for human osteosarcoma.

Topics: Agar; Apoptosis; Bone Neoplasms; Carcinogenesis; Cell Culture Techniques; Cell Growth Processes; Down-Regulation; Gene Knockdown Techniques; Humans; Kruppel-Like Transcription Factors; Osteosarcoma; RNA, Small Interfering; Zinc Fingers

The molecular mechanism leading to the cancer metastasis to bone is poorly understood but yet determines prognosis and therapy. Here, we define a new molecular pathway that may account for the extraordinarily high osteotropism of prostate cancer. By using SPARC (secreted protein, acidic and rich in cysteine)-deficient mice and recombinant SPARC, we demonstrated that SPARC selectively supports the migration of highly metastatic relative to less metastatic prostate cancer cell lines to bone. Increased migration to SPARC can be traced to the activation of integrins alphaVbeta3 and alphaVbeta5 on tumor cells. Such activation is induced by an autocrine vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-2 loop on the tumor cells, which also supports the growth and proliferation of prostate cancer cells. A consequence of SPARC recognition by alphaVbeta5 is enhanced VEGF production. Thus, prostate cancer cells expressing VEGF/VEGFR-2 will activate alphaVbeta3 and alphaVbeta5 on their surface and use these integrins to migrate toward SPARC in bone. Within the bone environment, SPARC engagement of these integrins will stimulate growth of the tumor and further production of VEGF to support neoangiogenesis, thereby favoring the development of the metastatic tumor. Supporting this model, activated integrins were found to colocalize with VEGFR-2 in tissue samples of metastatic prostate tumors from patients.

Topics: Agar; Animals; Bone and Bones; Bone Neoplasms; Cell Division; Cell Movement; Flow Cytometry; Humans; Immunohistochemistry; Integrin alphaVbeta3; Integrins; Male; Mice; Models, Biological; Neoplasm Metastasis; Neoplasm Transplantation; Osteonectin; Prostatic Neoplasms; Receptors, Vitronectin; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; Tumor Cells, Cultured; Vascular Endothelial Growth Factor Receptor-2

Breast cancer has a predilection for spreading to bone. The mechanism of preferential metastasis of breast cancer to bone is unknown. We hypothesize that breast cancer cells that develop bone metastases have the capacity to facilitate their colonization in bone. To examine this hypothesis, we established bone-seeking (MDA-231BO) and brain-seeking (MDA-231BR) clones of the human breast cancer cell line MDA-MB-231 by repeated sequential passages in nude mice and in vitro of metastatic cells obtained from bone and brain metastases, respectively. These clones were examined for distinguishing biological characteristics and compared with the MDA-231 parental cells (MDA-231P) in vivo and in vitro. Both the MDA-231BR and the MDA-231BO showed identical tumorigenicity to MDA-231P at the orthotopic site. MDA-231P that was inoculated into the heart developed metastases in bone, brain, ovary, and adrenal glands. On the other hand, MDA-231BO exclusively metastasized to bone with larger osteolytic lesions than MDA-231P. MDA-231BR exclusively disseminated to brain and failed to develop bone metastases. In culture, MDA-231BO produced greater amounts of parathyroid hormone-related protein (PTH-rP) than MDA-231BR and MDA-231P in the absence or presence of transforming growth factor beta (TGF-beta). Furthermore, the anchorage-independent growth of MDA- 231BO in soft agar was not inhibited by TGF-beta, whereas TGF-beta profoundly inhibited the growth of MDA-231P and MDA-231BR. Insulin-like growth factor I (IGF-I) markedly promoted the anchorage-independent growth of MDA-231BO, whereas marginal or no stimulation was observed in MDA-231BR or MDA-231P, respectively. Our data suggest that these phenotypic changes allow breast cancer cells to promote osteoclastic bone resorption, survive, and proliferate in bone, which consequently leads to the establishment of bone metastases.

Topics: Agar; Animals; Bone and Bones; Bone Neoplasms; Brain; Brain Neoplasms; Breast Neoplasms; Cell Adhesion; Cell Culture Techniques; Cell Division; Chemotaxis; Clone Cells; Female; Gene Expression; Humans; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Mammary Neoplasms, Experimental; Mice; Mice, Nude; Neoplasms, Experimental; Parathyroid Hormone-Related Protein; Plasminogen Activator Inhibitor 1; Promoter Regions, Genetic; Protein Biosynthesis; Signal Transduction; Transcriptional Activation; Transforming Growth Factor beta; Transforming Growth Factor beta1; Tumor Cells, Cultured

Thirty-one bone marrow aspirations were performed on patients with prostatic carcinoma metastatic to bone. After separation over a Ficoll-Hypaque gradient viable nucleated cells were cultured in semisolid agar. Colony formation occurred in 14 of 27 (52%) nonbacterially contaminated cultures. Characterization of cells from the colonies showed them to be consistent with malignant prostate cells. After staining, these cells were periodic acid-Schiff positive, prostatic acid phosphatase positive, and prostatic specific antigen positive. Other studies demonstrated the cells to be karyotypically abnormal, ultrastructurally similar to epithelial cells, and capable of secondary colony formation. Three bone marrow aspirate specimens did not have metastatic prostatic carcinoma detected by standard methods but did demonstrate colony formation. However, colony formation was most frequently seen when a radionuclide scan was positive at the aspiration site and when tumor cells were microscopically detectable by Wright staining of a smeared aspirate. The potential utility of colony forming cultures in prostate cancer is discussed. In working with bone marrow aspirates, additional cell separation procedures may be required to calculate and maximize plating efficiencies.

Topics: Agar; Biopsy; Bone Marrow; Bone Neoplasms; Carcinoma; Cells, Cultured; Humans; Karyotyping; Male; Microscopy, Electron; Neoplasm Metastasis; Prostatic Neoplasms

Topics: Adolescent; Adult; Agar; Bone Neoplasms; Child; Culture Techniques; Electrophoresis; Female; Fetus; Gels; Giant Cell Tumors; Humans; Isoenzymes; L-Lactate Dehydrogenase; Male; Middle Aged; Osteosarcoma; Pregnancy

Topics: Agar; Alkaline Phosphatase; Bile; Bone Diseases; Bone Neoplasms; Child; Clinical Enzyme Tests; Electrophoresis; Hodgkin Disease; Humans; Jaundice; Jaundice, Obstructive; Liver Diseases; Liver Neoplasms; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Osteitis Deformans; Sarcoma