RESUMO
Neovascularization, an essential step for tumor progression and metastasis development, can be modulated by the presence of macrophages (Mps) in the tumor microenvironment. The ability of Mps to regulate the angiogenicity of the LMM3 tumor cell line was studied. Peritoneal Mps from LMM3 tumor-bearing mice (TMps) potentiate in vivo LMM3 angiogenicity. These results were confirmed by CD31 immunoblotting assays. The activity of TMps depended on nitric oxide synthase (NOS) and arginase (A) activity. By immunoblotting we evidenced that AI and AII isoforms were up-regulated in TMps while the inducible and neuronal NOS isoforms were highly expressed in normal Mps. TMps might positively modulate tumor growth by stimulating angiogenic cascade mainly through polyamine synthesis.
Assuntos
Arginina/metabolismo , Macrófagos Peritoneais/metabolismo , Neoplasias Experimentais/irrigação sanguínea , Neoplasias Experimentais/metabolismo , Neovascularização Patológica , Animais , Arginase/fisiologia , Feminino , Isoenzimas/metabolismo , Macrófagos Peritoneais/enzimologia , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/enzimologia , Óxido Nítrico Sintase/fisiologia , Células Tumorais CultivadasAssuntos
Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Neoplasias Encefálicas , Moléculas de Adesão Celular Neuronais/sangue , Biomarcadores Tumorais/sangue , Neoplasias Encefálicas , Estudos de Casos e Controles , Ependimoma , Glioma , Neoplasias Pulmonares , Melanoma , Meningioma , Moléculas de Adesão Celular Neuronais , Biomarcadores Tumorais , Neoplasias Hipofisárias , Isoformas de Proteínas , Neoplasias do Colo do ÚteroAssuntos
Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Encefálicas/diagnóstico , Moléculas de Adesão Celular Neuronais/sangue , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Neoplasias Encefálicas/secundário , Moléculas de Adesão Celular Neuronais/diagnóstico , Biomarcadores Tumorais/diagnóstico , Neoplasias Hipofisárias/patologia , Neoplasias Pulmonares/patologia , Neoplasias do Colo do Útero/patologia , Melanoma/patologia , Glioma , Ependimoma , Meningioma , Isoformas de ProteínasRESUMO
Experimental transplantation of embryonic nervous cells in the central nervous system demonstrates that these precursor cells can be used to repair damaged cells in neurodegenerative diseases. However, the use of cells from embryos is still controversial and alternative ethically accepted sources are needed to overcome the inherent problems. Several sources have been proposed such as bone marrow cells, olfactory bulb cells and astrocytes. We suggest the use of neuronal precursor cells from the nasal olfactory mucosa as an alternative source for transplantation therapy, since these peripheric cells exhibit stem cell characteristics.
Assuntos
Neurônios/transplante , Transplante de Células-Tronco , Sistema Nervoso Central/citologia , Humanos , Doenças Neurodegenerativas/cirurgia , Neurônios/fisiologia , Mucosa Olfatória/inervaçãoRESUMO
Experimental transplantation of embryonic nervous cells in the central nervous system demonstrates that these precursor cells can be used to repair damaged cells in neurodegenerative diseases. However, the use of cells from embryos is still controversial and alternative ethically accepted sources are needed to overcome the inherent problems. Several sources have been proposed such as bone marrow cells, olfactory bulb cells and astrocytes. We suggest the use of neuronal precursor cells from the nasal olfactory mucosa as an alternative source for transplantation therapy, since these peripheric cells exhibit stem cell characteristics.
RESUMO
We established and characterized a new mammary tumor cell line, LM2, derived from M2 mammary adenocarcinoma which spontaneously appeared in a BALB/c female mouse. The LM2 cell line has been maintained in culture for more than 40 passages and grows as poorly differentiated elongated cells. Ultrastructural and immunocytochemistry analysis revealed characteristic features of adenocarcinoma. Cytogenetic studies showed that LM2 cells are fundamentally hypotetraploid. They express metalloproteinases (MMP) and show high levels of plasminogen activator type urokinase (uPA). They were sensitive to nitric oxide (NO)-mediated cytotoxicity when NO derived from an exogenous donor. In vivo, although LM2 cells were able to grow in the lungs, they could not metastasize to the same target organ from s.c. primary tumors. The LM2 mouse mammary adenocarcinoma cell line is a suitable model to examine different aspects of tumor biology, in particular those related to the different pathways involved in the metastatic cascade and in the cytotoxicity mediated by NO.
Assuntos
Adenocarcinoma/patologia , Neoplasias Mamárias Experimentais/patologia , Células Tumorais Cultivadas , Adenocarcinoma/química , Adenocarcinoma/secundário , Aneuploidia , Animais , Feminino , Fibroblastos/patologia , Neoplasias Pulmonares/secundário , Neoplasias Mamárias Experimentais/química , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica , Invasividade Neoplásica , Metástase Neoplásica , Proteínas de Neoplasias/análise , Transplante de Neoplasias , Óxido Nítrico/farmacologia , Células Tumorais Cultivadas/química , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/ultraestrutura , Ativador de Plasminogênio Tipo Uroquinase/análiseRESUMO
This article is a bibliographic review concerning the scientific advances in nervous tissue transplantation in experimental animals and in humans as applied to neurodegenerative diseases, particularly Parkinson's disease. Data show the possibility that the transplantation of nervous tissue may alleviate the typical symptoms of some of these diseases. Since the first trials in 1890, there has been a remarkable progress in this field, encouraging the idea that nervous tissue transplantation may be considered in clinical practice.
Assuntos
Tecido Nervoso/transplante , Doenças Neurodegenerativas/cirurgia , Neurônios/transplante , Animais , Encéfalo/cirurgia , Humanos , Doença de Parkinson/cirurgia , Ratos , Transplante Heterólogo/métodosRESUMO
This article is a bibliographic review concerning the scientific advances in nervous tissue transplantation in experimental animals and in humans as applied to neurodegenerative diseases, particularly Parkinsons disease. Data show the possibility that the transplantation of nervous tissue may alleviate the typical symptoms of some of these diseases. Since the first trials in 1890, there has been a remarkable progress in this field, encouraging the idea that nervous tissue transplantation may be considered in clinical practice.
RESUMO
The ability of tumor cells to respond to microenvironmental factors present in the target organ determines in part the successful development of a metastasis. In a previous work it was demonstrated that the conditioned medium (CM) from lungs of normal mice stimulates in vitro migration, proliferation and uPA activity of cells from a murine mammary adenocarcinoma moderately metastatic to lung. This CM also enhanced local and metastatic tumor growth. Here, we show that lung CM enhanced neovascularization when inoculated together with LM3 tumor cells into the skin of syngeneic mice. A similar tumor-induced angiogenesis response was obtained when lung CM was injected systemically. Western blot analysis of lung CM revealed the presence of some laminin fragments containing the sequence SIKVAV. To determine whether those molecules were responsible for the observed angiogenic effects, the CM was depleted of the peptides containing the SIKVAV sequence. We observed that the SIKVAV-depleted lung CM lost its ability to induce an enhancement of the tumor neovascular response. Our results suggest a role for the target organ in facilitating the neovascularization of tumor cells, probably through the participation of active peptides derived from the proteolytic degradation of the basement membrane component laminin.
Assuntos
Laminina/farmacologia , Pulmão/fisiologia , Neovascularização Patológica , Animais , Meios de Cultivo Condicionados , Pulmão/química , Linfócitos/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Fragmentos de Peptídeos/farmacologia , Células Tumorais CultivadasRESUMO
T-lymphocytes from tumour-bearing mice are able to trigger the angiogenic cascade. Since it is known that tumour growth produces reactive oxygen species (ROS), the aim of this study was to evaluate the role of hydrogen peroxide (H2O2) on the activation of lymphocytes and their induction of this vascular response. Studies on lymphocytes, stimulated in vitro by ROS to induce angiogenesis, showed that only the enzyme catalase (CAT) could block the activation. The incubation of normal lymphocytes with H2O2 stimulated these cells to induce angiogenesis. The administration of H2O2 or an oxidative stress-producing drug (doxorubicin) to normal mice activated in vivo angiogenesis. In tumour-bearing mice, high levels of lipid peroxidation products were observed in the spleen, but not in the liver or kidney. Moreover, when the ROS scavenger enzyme activities (superoxide dismutase (SDM) and CAT) were determined, we observed low CAT activity in normal spleens, reflected in a high SDM/CAT ratio, when compared to liver or kidney values. We also showed an increasing value of the SDM/CAT ratio with tumour growth. These results strongly suggest that H2O2 could be involved in the mechanisms of lymphocyte activation and their induction of angiogenesis during tumour growth.