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The International Journal of... Mar 1989In this paper we discuss studies on basement membrane and interstitial matrix molecules in early development and teratocarcinoma differentiation. In the early embryo a... (Review)
Review
In this paper we discuss studies on basement membrane and interstitial matrix molecules in early development and teratocarcinoma differentiation. In the early embryo a compartmentalization of newly formed cell types takes place immediately by formation of basement membranes. The stage-specific developmental appearance of extracellular matrix molecules such as type IV collagen, laminin, entactin, fibronectin and proteoglycans seems to reflect a diversified role of extracellular matrices already in the earliest stages of development. In teratocarcinoma cultures the appearance and composition of extracellular matrices during the differentiation of endoderm cells closely resembles that found in the early embryo. Also in this respect the teratocarcinoma system can be used as a model for studies on early development. In later developmental phenomena other matrix molecules can also be of importance. Merosin, a novel tissue-specific basement membrane-associated protein that appears during muscle and nerve maturation is an example of such molecules.
Topics: Animals; Basement Membrane; Cell Transformation, Neoplastic; Extracellular Matrix; Muscles; Nervous System; Structure-Activity Relationship; Tumor Cells, Cultured
PubMed: 2485704
DOI: No ID Found -
Cancers Jul 2022Tumor growth and metastasis strongly rely on cell-cell communication. One of the mechanisms by which tumor cells communicate involves the release and uptake of lipid...
Tumor growth and metastasis strongly rely on cell-cell communication. One of the mechanisms by which tumor cells communicate involves the release and uptake of lipid membrane encapsulated particles full of bioactive molecules, called extracellular vesicles (EVs). EV exchange between cancer cells may induce phenotype changes in the recipient cells. Our work investigated the effect of EVs released by teratocarcinoma cells on glioblastoma (GBM) cells. EVs were isolated by differential centrifugation and analyzed through Western blot, nanoparticle tracking analysis, and electron microscopy. The effect of large EVs on GBM cells was tested through cell migration, proliferation, and drug-sensitivity assays, and resulted in a specific impairment in cell migration with no effects on proliferation and drug-sensitivity. Noticeably, we found the presence of the EGF-CFC founder member CRIPTO on both small and large EVs, in the latter case implicated in the EV-mediated negative regulation of GBM cell migration. Our data let us propose a novel route and function for CRIPTO during tumorigenesis, highlighting a complex scenario regulating its effect, and paving the way to novel strategies to control cell migration, to ultimately improve the prognosis and quality of life of GBM patients.
PubMed: 35954365
DOI: 10.3390/cancers14153700 -
The International Journal of... Mar 1989Embryonal carcinoma (EC) cells, which are the malignant stem cells of teratocarcinomas, are considered similar to early embryo cells. The EC cells can be grown in vitro,... (Review)
Review
Embryonal carcinoma (EC) cells, which are the malignant stem cells of teratocarcinomas, are considered similar to early embryo cells. The EC cells can be grown in vitro, and many of them can be experimentally induced to differentiate; upon differentiation, the cells become benign. Here we review some of the changes that take place in the cellular and molecular characteristics of murine F9 EC cells as they differentiate into endodermal cells. Upon differentiation of F9 cells, distinct changes occur in their cell surface molecules, cytoskeleton-associated proteins and cell adhesion properties. Simultaneously, the rate of cell proliferation decreases due to a dramatic increase in duration of G1 and S phases of the cell cycle. The changes in gene expression and cell behavior occurring during endodermal differentiation of EC cells closely resemble those occurring when the endoderm differentiates in the embryo. Teratocarcinoma stem cell lines may thus be exploited to enhance understanding of both teratoma-type neoplasms and embryonic development.
Topics: Animals; Cell Adhesion; Cell Differentiation; Cytoskeletal Proteins; Embryonal Carcinoma Stem Cells; Mice; Models, Biological; Neoplastic Stem Cells; Teratoma
PubMed: 2485690
DOI: No ID Found -
Annals of Oncology : Official Journal... Jan 1997Sparse data are available with regard to the incidence, clinical characteristics, therapeutic management and prognosis of male patients with germ cell tumors, who... (Comparative Study)
Comparative Study Review
BACKGROUND
Sparse data are available with regard to the incidence, clinical characteristics, therapeutic management and prognosis of male patients with germ cell tumors, who relapse more than two years after completion of cisplatin-based chemotherapy.
PATIENTS AND METHODS
A review of 530 patients treated at two institutions from 1978 to April 1994 was conducted. Twenty-five cases of late relapse were identified. Cumulative risk of late relapse was calculated according to the Kaplan-Meier method.
RESULTS
418 of 523 patients (80%) who received their first-line treatment at our institutions were relapse-free at two years. Among these 418 patients 18 cases (4.3%) developed a late relapse. The cumulative risk of late relapse was 1.1% at five years and 4.0% at ten years excluding patients with prior early relapses who carried risks of 9.4% and 29%, respectively (P < 0.0001). No case of late relapse was observed among patients receiving adjuvant chemotherapy. The risk of late relapse was lower in patients with good-risk non-seminomatous germ cell tumors than in poor-risk patients according to Medical Research Council criteria (P < 0.01). Seven further patients were referred from other institutions for treatment of late relapse. At a median follow-up of 38 months (range, 3 to 121) after treatment of late relapse 9 of 25 patients (36%) are continuously disease-free. Six of these nine patients had surgical resection of carcinoma or teratoma as a component of their therapy.
CONCLUSION
The incidence of late relapse after cisplatin-based chemotherapy of germ cell tumors is related to initial tumor burden and is somewhat higher than previously expected. Chemotherapy seems to have only minor curative potential, but localized resectable disease can be cured by surgery. Annual follow-up evaluations allow to detect the majority of late relapses at an asymptomatic stage and should be extended throughout the patient's life.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bleomycin; Carcinoma, Embryonal; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Etoposide; Fatal Outcome; Germinoma; Humans; Life Tables; Lung Neoplasms; Lymphatic Metastasis; Male; Mediastinal Neoplasms; Neoplasm Metastasis; Neoplasm Recurrence, Local; Orchiectomy; Pelvic Neoplasms; Remission Induction; Retroperitoneal Neoplasms; Retrospective Studies; Salvage Therapy; Teratocarcinoma; Testicular Neoplasms; Treatment Failure; alpha-Fetoproteins
PubMed: 9093706
DOI: 10.1023/a:1008253323854 -
The International Journal of... Mar 1993Using mouse teratocarcinoma system, we found a novel retinoic acid responsive gene. Midkine (MK), the product of the gene is a secreted, heparin-binding protein of... (Review)
Review
Using mouse teratocarcinoma system, we found a novel retinoic acid responsive gene. Midkine (MK), the product of the gene is a secreted, heparin-binding protein of molecular weight 14,000. MK gene is intensely expressed in the midgestation period, and in the adult mouse, the kidney is the principal site of its expression. MK and pleiotrophin have 50% sequence identity and constitute a new protein family regulating growth and differentiation. They share neurite outgrowth activity; other activities, either specific for one or common to both, have been reported. Furthermore, MK is of significant interest in cancer biology.
Topics: Amino Acid Sequence; Animals; Carrier Proteins; Cell Differentiation; Cell Division; Cells, Cultured; Cytokines; DNA; Gene Expression Regulation; Humans; Mice; Midkine; Molecular Sequence Data; Protein Sorting Signals; Sequence Homology, Amino Acid; Tretinoin
PubMed: 8507561
DOI: No ID Found -
The Journal of Biological Chemistry Mar 2018The pluripotency-controlling stem-cell protein SRY-box 2 (SOX2) plays a pivotal role in maintaining the self-renewal and pluripotency of embryonic stem cells and also of... (Comparative Study)
Comparative Study
The pluripotency-controlling stem-cell protein SRY-box 2 (SOX2) plays a pivotal role in maintaining the self-renewal and pluripotency of embryonic stem cells and also of teratocarcinoma or embryonic carcinoma cells. SOX2 is monomethylated at lysine 119 (Lys-119) in mouse embryonic stem cells by the SET7 methyltransferase, and this methylation triggers ubiquitin-dependent SOX2 proteolysis. However, the molecular regulators and mechanisms controlling SET7-induced SOX2 proteolysis are unknown. Here, we report that in human ovarian teratocarcinoma PA-1 cells, methylation-dependent SOX2 proteolysis is dynamically regulated by the LSD1 lysine demethylase and a methyl-binding protein, PHD finger protein 20-like 1 (PHF20L1). We found that LSD1 not only removes the methyl group from monomethylated Lys-117 (equivalent to Lys-119 in mouse SOX2), but it also demethylates monomethylated Lys-42 in SOX2, a reaction that SET7 also regulated and that also triggered SOX2 proteolysis. Our studies further revealed that PHF20L1 binds both monomethylated Lys-42 and Lys-117 in SOX2 and thereby prevents SOX2 proteolysis. Down-regulation of either LSD1 or PHF20L1 promoted SOX2 proteolysis, which was prevented by SET7 inactivation in both PA-1 and mouse embryonic stem cells. Our studies also disclosed that LSD1 and PHF20L1 normally regulate the growth of pluripotent mouse embryonic stem cells and PA-1 cells by preventing methylation-dependent SOX2 proteolysis. In conclusion, our findings reveal an important mechanism by which the stability of the pluripotency-controlling stem-cell protein SOX2 is dynamically regulated by the activities of SET7, LSD1, and PHF20L1 in pluripotent stem cells.
Topics: Amino Acid Substitution; Animals; Cell Line, Tumor; Cells, Cultured; Chromosomal Proteins, Non-Histone; Embryonic Stem Cells; Female; HEK293 Cells; Histone Demethylases; Histone-Lysine N-Methyltransferase; Humans; Methylation; Mice, Inbred C57BL; Mutation; Neoplasm Proteins; Ovarian Neoplasms; Protein Processing, Post-Translational; Protein Stability; Proteolysis; RNA Interference; Recombinant Fusion Proteins; SOXB1 Transcription Factors; Teratocarcinoma
PubMed: 29358331
DOI: 10.1074/jbc.RA117.000342 -
Case Reports in Oncology 2023Teratocarcinoma is one type of testis cancer that can be represented in the youth population and usually shows itself with swelling of the testis and edema and a rise of...
Teratocarcinoma is one type of testis cancer that can be represented in the youth population and usually shows itself with swelling of the testis and edema and a rise of BHCG and alpha-fetoprotein, but spontaneous rupture is a rare manifestation. A 23-year-old man was referred to the Sina Hospital with complaints of testis pain and swelling. Laboratory findings were alpha f.p more than 2,000, BHCG titer 255.21, and LDH 504. Sonography findings showed the right testis had been detected with a heterogeneous mass with vascularity and cystic area with microcalcification, measuring 76*69 mm. During surgery, we faced rupture tumor that was unusual and rare. The radical orchidectomy was done successfully without any complications. After the surgery, pathology showed teratocarcinoma of the right testis, and a 6-month observation and follow-up were done without any complication.
PubMed: 37123610
DOI: 10.1159/000530502 -
PloS One 2013Antiangiogenic treatments are beginning to give promising outcomes in many vascular diseases including tumor angiogenesis. In this current study the antiangiogenic and...
OBJECT
Antiangiogenic treatments are beginning to give promising outcomes in many vascular diseases including tumor angiogenesis. In this current study the antiangiogenic and pro-apoptotic actions of α1(IV)NC1 and its N- and C- peptides α1S1(IV)NC1, α1S2(IV)NC1 were investigated in-vitro and in-vivo.
STUDY METHOD
Endothelial cells (ECs) were treated with α1(IV)NC1, α1S1(IV)NC1, α1S2(IV)NC1 and in-vitro proliferation, migration, tube formation and apoptotic assays were executed. FasL, Fas, Caspase-8, -3 and PARP activations were studied using immunoblotting analysis using specific antibodies. Also the in-vivo antiangiogenic and pro-apoptotic effects were tested using α1(IV)NC1 in a mice model.
RESULTS
Like α1(IV)NC1, its N- and C- terminal α1S2(IV)NC1 and α1S1(IV)NC1 domains posses anti-proliferative, pro-apoptotic activity and inhibit ECs migration and tube formation in-vitro. Both α1S1(IV)NC1 and α1S2(IV)NC1 domains promote apoptosis by activating FasL and down stream apoptotic events including activation of caspase-8, -3 and PARP cleavage in a dose dependent manner in-vitro in ECs. Tumors in mice showed apoptotic TUNEL positive microvasculature upon α1(IV)NC1 treatment, indicating inhibition of tumor angiogenesis and tumor growth. Further, the antitumor activity of α1(IV)NC1 was abrogated when caspase-3 inhibitor was used. These results conform additional properties of α1(IV)NC1 as an endogenous angioinhibitor that induces apoptosis in-vitro and in-vivo by activating FasL mediated caspase-3.
SIGNIFICANCE
α1(IV)NC1 and its N- and C- terminal α1S1(IV)NC1 and α1S2(IV)NC1 domains also posses pro-apoptotic and angioinhibitory activity in-vitro and in-vivo. α1(IV)NC1 regulates tumor angiogenesis by activating FasL mediated apoptosis in-vitro and in-vivo. These results demonstrate that α1(IV)NC1 and its peptides inhibit neo-vascular diseases.
Topics: Angiogenesis Inhibitors; Animals; Apoptosis; Caspase 3; Caspase 8; Cell Adhesion; Cell Line, Tumor; Cell Movement; Cell Proliferation; Collagen Type IV; Endothelial Cells; Endothelium, Vascular; Fas Ligand Protein; Gene Expression Regulation, Neoplastic; Humans; Mice; Neovascularization, Pathologic; Poly(ADP-ribose) Polymerases; Protein Isoforms; Signal Transduction; Skin Neoplasms; Teratocarcinoma; fas Receptor
PubMed: 24324608
DOI: 10.1371/journal.pone.0080555 -
The American Journal of Pathology Sep 1998Complement-mediated lysis of cancer cells growing in three-dimensional aggregates involves factors that are not associated with the killing of cells in suspension. We...
Complement-mediated lysis of cancer cells growing in three-dimensional aggregates involves factors that are not associated with the killing of cells in suspension. We have used multicellular tumor spheroids established from breast carcinoma (T47D) and ovarian teratocarcinoma (PA-1) cell lines as models to study complement-mediated destruction of micrometastases and small solid tumors. We found that significant killing of microtumors treated with an antitumor antibody and a specific monoclonal antibody (YTH53.1) against the complement lysis inhibitor protectin (CD59) started to occur after a 1 to 2-hour lag phase. After an overnight incubation, the microtumors became totally infiltrated by the YTH53.1 monoclonal antibody and C1q, whereas C3 and C5b-9 penetrated as a frontier to the peripheral cell layers. A 51Cr release assay showed that during a 24-hour pulsed treatment with complement, 33% of cells in the spheroids were killed, and the average tumor volume decreased by 28%. According to propidium iodide staining, complement exposure resulted in killing and peeling off of the outermost tumor cells.
Topics: Antibodies, Monoclonal; Antibodies, Neoplasm; Antibody-Dependent Cell Cytotoxicity; Breast Neoplasms; CD59 Antigens; Carcinoma, Ductal, Breast; Cell Death; Complement Activation; Complement System Proteins; Cytotoxicity, Immunologic; Female; Fluorescent Antibody Technique, Indirect; Humans; Ovarian Neoplasms; Spheroids, Cellular; Teratocarcinoma; Tumor Cells, Cultured
PubMed: 9736033
DOI: 10.1016/S0002-9440(10)65626-X -
Medecine Sciences : M/S Oct 2010More than 20 years ago, the finding of a population of cells with the ability of self-renewal and differentiation inside teratocarcinomas (embryonic carcinoma cells)... (Review)
Review
More than 20 years ago, the finding of a population of cells with the ability of self-renewal and differentiation inside teratocarcinomas (embryonic carcinoma cells) would allow their direct derivation from preimplantation embryos (embryonic stem cells, ESC). The phenomenal pluripotency properties of those cells and the therapeutical potential of their human counterparts triggered a massive interest from the scientific community. The research on the field of pluripotent stem cells improved a lot and many ES-like pluripotent stem cells of several embryonic and adult sources were described. Next step has been the reprogramming of terminally differentiated cells into embryonic cells, with the aim to produce patient-specific stem cells. The recent breakthrough has been the in vitro reprogramming of adult cells into ES cell-like cells named induced pluripotent stem cells (iPSC), using four transcription factors (Oct4, Sox2, Klf4, c-Myc). Even though some challenges remain, we are now one step closer to the eventuality to use these cells for clinical purposes. In this review we propose to analyse the several pluripotent stem cells existing today.
Topics: Animals; Blastocyst; Cell Differentiation; Cord Blood Stem Cell Transplantation; Humans; Induced Pluripotent Stem Cells; Kruppel-Like Factor 4; Mice; Pluripotent Stem Cells; Stem Cell Transplantation; Teratoma; Transcription Factors
PubMed: 20929676
DOI: 10.1051/medsci/20102610848