RESUMO
Lung cancer is the leading cause of cancer mortality around the world. The lack of detailed understanding of the cellular and molecular mechanisms participating in the lung tumor progression restrains the development of efficient treatments. Recently, by using state-of-the-art technologies, including in vivo sophisticated Cre/loxP technologies in combination with lung tumor models, it was revealed that osteoblasts activate neutrophils that promote tumor growth in the lung. Strikingly, genetic ablation of osteoblasts abolished lung tumor progression via interruption of SiglecFhigh-expressing neutrophils supply to the tumor microenvironment. Interestingly, SiglecFhigh neutrophil signature was associated with worse lung adenocarcinoma patients outcome. This study identifies novel cellular targets for lung cancer treatment. Here, we summarize and evaluate recent advances in our understanding of lung tumor microenvironment.
Assuntos
Comunicação Celular/fisiologia , Neoplasias Pulmonares/patologia , Neutrófilos/patologia , Osteoblastos/patologia , Animais , Humanos , Microambiente TumoralRESUMO
The premetastatic niche formed by primary tumor-derived molecules contributes to fixation of cancer metastasis. The design of efficient therapies is limited by the current lack of knowledge about the details of cellular and molecular mechanisms involved in the premetastatic niche formation. Recently, the role of pericytes in the premetastatic niche formation and lung metastatic tropism was explored by using state-of-the-art techniques, including in vivo lineage-tracing and mice with pericyte-specific KLF4 deletion. Strikingly, genetic inactivation of KLF4 in pericytes inhibits pulmonary pericyte expansion and decreases metastasis in the lung. Here, we summarize and evaluate recent advances in the understanding of pericyte contribution to premetastatic niche formation. Cancer Res; 78(11); 2779-86. ©2018 AACR.
Assuntos
Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Pericitos/patologia , Animais , Humanos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/genética , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologiaRESUMO
Healing is a vital response important for the re-establishment of the skin integrity following injury. Delayed or aberrant dermal wound healing leads to morbidity in patients. The development of therapies to improve dermal healing would be useful. Currently, the design of efficient treatments is stalled by the lack of detailed knowledge about the cellular and molecular mechanisms involved in wound healing. Recently, using state-of-the-art technologies, it was revealed that macrophages signal via GPNMB to mesenchymal stem cells, accelerating skin healing. Strikingly, transplantation of macrophages expressing GPNMB improves skin healing in GPNMB-mutant mice. Additionally, topical treatment with recombinant GPNMB restored mesenchymal stem cells recruitment and accelerated wound closure in the diabetic skin. From a drug development perspective, this GPNMB is a new candidate for skin healing.
Assuntos
Células-Tronco Mesenquimais , Cicatrização , Animais , Células Cultivadas , Proteínas do Olho , Glicoproteínas , Humanos , Macrófagos , Glicoproteínas de Membrana , Camundongos , PeleRESUMO
Glioblastoma multiforme is the most common and aggressive primary brain tumor, with an extremely poor prognosis. The lack of detailed knowledge about the cellular and molecular mechanisms involved in glioblastoma development restricts the design of efficient therapies. A recent study using state-of-art technologies explores the role of pericytes in the glioblastoma microenvironment. Glioblastoma-activated pericytes develop an immunosuppressive phenotype, reducing T-cell activation through the induction of an anti-inflammatory response. Strikingly, pericytes support glioblastoma growth in vitro and in vivo. Here, we describe succinctly the results and implications of the findings reported in pericytes' and glioblastomas' biology. The emerging knowledge from this study will be essential for the treatment of brain tumors.
Assuntos
Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Glioblastoma/imunologia , Glioblastoma/patologia , Imunomodulação , Pericitos/imunologia , Animais , Biomarcadores , Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Humanos , Tolerância Imunológica , Pericitos/metabolismo , Fenótipo , Transdução de Sinais , Evasão Tumoral/imunologia , Microambiente Tumoral/imunologiaRESUMO
Pericytes are defined by their anatomical location encircling blood vessels' walls with their long projections. The exact embryonic sources of cerebral pericytes remain poorly understood, especially because of their recently revealed diversity. Yamamoto et al. (Sci Rep 7(1):3855, 2017) using state-of-the-art techniques, including several transgenic mice models, reveal that a subpopulation of brain pericytes are derived from phagocytic macrophages during vascular development. This work highlights a new possible ancestor of brain pericytes. The emerging knowledge from this research may provide new approaches for the treatment of several neurodevelopmental disorders in the future.
Assuntos
Encéfalo/patologia , Macrófagos/patologia , Transtornos do Neurodesenvolvimento/patologia , Pericitos/patologia , Animais , Encéfalo/irrigação sanguínea , Humanos , Camundongos Transgênicos , Transtornos do Neurodesenvolvimento/diagnósticoRESUMO
Bone marrow fibrosis is a reactive process, and a central pathological feature of primary myelofibrosis. Revealing the origin of fibroblastic cells in the bone marrow is crucial, as these cells are considered an ideal, and essential target for anti-fibrotic therapy. In 2 recent studies, Decker et al. (2017) and Schneider et al. (2017), by using state-of-the-art techniques including in vivo lineage-tracing, provide evidence that leptin receptor (LepR)-expressing and Gli1-expressing cells are responsible for fibrotic tissue deposition in the bone marrow. However, what is the relationship between these 2 bone marrow cell populations, and what are their relative contributions to bone marrow fibrosis remain unclear. From a drug development perspective, these works bring new cellular targets for bone marrow fibrosis.
Assuntos
Células da Medula Óssea/patologia , Medula Óssea/patologia , Fibroblastos/patologia , Mielofibrose Primária/metabolismo , Receptores para Leptina/metabolismo , Animais , Dissidências e Disputas , HumanosAssuntos
Glândulas Suprarrenais , Células Cromafins , Células de Schwann , Células-Tronco , Glândulas Suprarrenais/citologia , Glândulas Suprarrenais/metabolismo , Animais , Células Cromafins/citologia , Células Cromafins/metabolismo , Humanos , Células de Schwann/citologia , Células de Schwann/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismoRESUMO
Niches are specialized microenvironments that regulate stem cells' activity. The neural stem cell (NSC) niche defines a zone in which NSCs are retained and produce new cells of the nervous system throughout life. Understanding the signaling mechanisms by which the niche controls the NSC fate is crucial for the success of clinical applications. In a recent study, Sato and colleagues, by using state-of-the-art techniques, including sophisticated in vivo lineage-tracing technologies, provide evidence that endothelial amyloid precursor protein (APP) is an important component of the NSC niche. Strikingly, depletion of APP increased NSC proliferation in the subventricular zone, indicating that endothelial cells negatively regulate NSCs' growth. The emerging knowledge from this research will be important for the treatment of several neurological diseases.
Assuntos
Células-Tronco Adultas , Células-Tronco Neurais , Adulto , Encéfalo , Células Endoteliais , Humanos , Nicho de Células-TroncoRESUMO
Neural stem cells (NSCs) are a heterogeneous population of cells that generate new neurons in adult animals. Recently in Science, Paul et al. (2017) show that hypothalamic neurons control activation of a subset of NSCs in response to feeding, providing insights into how physiological cues may influence stem cell activation.
Assuntos
Células-Tronco Adultas/citologia , Células-Tronco Neurais/citologia , Adulto , Animais , Neurogênese , Neurônios/citologia , Nicho de Células-TroncoRESUMO
Prostate cancer cells metastasize to the bones, causing ectopic bone formation, which results in fractures and pain. The cellular mechanisms underlying new bone production are unknown. In a recent study, Lin and colleagues, by using state-of-the-art techniques, including prostate cancer mouse models in combination with sophisticated in vivo lineage-tracing technologies, revealed that endothelial cells form osteoblasts induced by prostate cancer metastasis in the bone. Strikingly, genetic deletion of osteorix protein from endothelial cells affected prostate cancer-induced osteogenesis in vivo. Deciphering the osteoblasts origin in the bone microenvironment may result in the development of promising new molecular targets for prostate cancer therapy.
Assuntos
Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Células Endoteliais/patologia , Osteoblastos/patologia , Osteogênese/fisiologia , Neoplasias da Próstata/patologia , Animais , Neoplasias Ósseas/metabolismo , Células Endoteliais/metabolismo , Humanos , Masculino , Osteoblastos/metabolismo , Neoplasias da Próstata/metabolismo , Microambiente Tumoral/fisiologiaRESUMO
Bone marrow fibrosis is a critical component of primary myelofibrosis in which normal bone marrow tissue and blood-forming cells are gradually replaced with scar tissue. The specific cellular and molecular mechanisms that cause bone marrow fibrosis are not understood. A recent study using state-of-the-art techniques, including in vivo lineage tracing, provides evidence that Gli1+ cells are the cells responsible for fibrotic disease in the bone marrow. Strikingly, genetic depletion of Gli1+ cells rescues bone marrow failure and abolishes myelofibrosis. This work introduces a new central cellular target for bone marrow fibrosis. The knowledge that emerges from this research will be important for the treatment of several malignant and nonmalignant disorders.