A5035786541- Cancer Cells and Metastasis
- Kruppel-like factors research
- Connective Tissue Growth Factor Research
- Muscle Physiology and Disorders
- Wnt/β-catenin signaling in development and cancer
- Periodontal Regeneration and Treatments
- TGF-β signaling in diseases
- Pleural and Pulmonary Diseases
- Immune cells in cancer
- Inflammatory Biomarkers in Disease Prognosis
- Cell Adhesion Molecules Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Prostate Cancer Treatment and Research
- Cancer Immunotherapy and Biomarkers
- Glycosylation and Glycoproteins Research
- Angiogenesis and VEGF in Cancer
- Adipose Tissue and Metabolism
- Immunotherapy and Immune Responses
- Chemokine receptors and signaling
- Exercise and Physiological Responses
- Genetic Neurodegenerative Diseases
- Connective tissue disorders research
- Occupational and environmental lung diseases
- Axon Guidance and Neuronal Signaling
- Histone Deacetylase Inhibitors Research
St. Jude Children's Research Hospital
2013-2023
Molecular Oncology (United States)
2022-2023
Massachusetts Institute of Technology
2011-2013
Howard Hughes Medical Institute
2012
Lahey Hospital and Medical Center
2010
TU Dresden
2008
Université du Québec à Montréal
2001
Significance Specialized microenvironments (or “niches”) are essential for metastasis, but how cancer cells and host contribute to their establishment remains poorly understood. Our study reveals that platelets granulocytes sequentially recruited disseminated tumor form “early metastatic niches” promote progression. Importantly, the recruitment of is not primarily due cell-derived signals rather relies on platelet-derived CXCL5/7 chemokines. Prevention granulocyte via inhibition receptor...
Abstract Skeletal muscle regeneration involves coordinated interactions between different cell types. Injection of platelet-rich plasma is circumstantially considered an aid to repair but whether platelets promote beyond their role in hemostasis remains unexplored. Here, we find that signaling via platelet-released chemokines early event necessary for mice. Platelet depletion reduces the levels platelet-secreted neutrophil chemoattractants CXCL5 and CXCL7/PPBP. Consequently, early-phase...
Abstract Epithelial-to-mesenchymal transition (EMT) is an important event during carcinoma progression and leads to increased tumor cell malignancy. Here, we show that vascular endothelial (VE)-cadherin induced EMT in mammary cells aberrantly expressed invasive human breast carcinomas. VE-cadherin enhanced the capacity of fibroblastoid proliferate, form cord-like structures, adhere cells, characteristics are key contributors their malignancy metastatic potential. Consistently, expression...
Skeletal muscle cell (myofiber) atrophy is a detrimental component of aging and cancer that primarily results from protein degradation via the proteasome ubiquitin ligases. Transcriptional upregulation some ligases contributes to myofiber atrophy, but little known about role most other play in this process. To address question, we have used RNAi screening Drosophila identify function > 320 evolutionarily conserved size regulation vivo. We find whereas for induces loss others (including N-end...
Skeletal muscle atrophy is a debilitating condition that occurs with aging and disease, but the underlying mechanisms are incompletely understood. Previous work determined common transcriptional changes occur in during induced by different stimuli. However, whether this holds true at proteome level remains largely unexplored. Here, we find that, contrary to earlier model, distinct atrophic stimuli (corticosteroids, cancer cachexia, aging) induce mRNA protein mice. Moreover, there widespread...
Platelets are a recognised potent source of transforming growth factor-β1 (TGFβ1), cytokine known to promote wound healing and regeneration by stimulating dermal fibroblast proliferation extracellular matrix deposition. Platelet lysate has been advocated as novel personalised therapeutic treat persistent wounds, although the precise platelet-derived factors responsible for these beneficial effects have not fully elucidated. The aim this study was investigate specific role TGFβ1 in cutaneous...
Abstract Decline in skeletal muscle cell size (myofiber atrophy) is a key feature of cancer-induced wasting (cachexia). In particular, atrophy the diaphragm, major responsible for breathing, an important determinant cancer-associated mortality. However, therapeutic options are limited. Here, we have used Drosophila transgenic screening to identify muscle-secreted factors (myokines) that act as paracrine regulators myofiber growth. Subsequent testing mouse myotubes revealed Fibcd1...
Metastases arise from rare cancer cells that successfully adapt to the diverse microenvironments encountered during dissemination through bloodstream and colonization of distant tissues. How acquire ability appropriately respond microenvironmental stimuli remains largely unexplored. Here, we report an epigenetic pliancy mechanism allows metastasize. We find a decline in activity transcriptional repressor ZBTB18 defines metastasis-competent mouse models. Restoration reduces chromatin...
Deregulation of cadherin expression, in particular the loss epithelial (E)-cadherin and gain neural (N)-cadherin, has been implicated carcinoma progression. We previously showed that endothelial cell-specific vascular (VE)-cadherin can be expressed aberrantly on tumor cells both human breast cancer experimental mouse mammary carcinoma. Functional analyses revealed VE-cadherin promotes cell proliferation invasion by stimulating transforming growth factor (TGF)-β signaling. Here, we...
Transforming growth factor-β1 (TGFβ1) is the key profibrotic cytokine in idiopathic pulmonary fibrosis (IPF), but primary source of this disease unknown. Platelets have abundant stores TGFβ1, although role these cells IPF ill-defined. In study, we investigated whether platelets, and specifically platelet-derived mediate progression. Patients with non-IPF patients were recruited to determine platelet reactivity, separate cohorts followed for mortality. To study TGFβ1 modulates (PF), mice a...
Abstract Platelets have important hemostatic functions in repairing blood vessels upon tissue injury. Cytokines, growth factors, and metabolites stored platelet α‐granules dense granules are released activation clotting. Emerging evidence indicates that such platelet‐derived signaling factors instrumental guiding regeneration. Here, we discuss the roles of platelet‐secreted skeletal muscle Chemokines secreted by platelets early phase after injury needed to recruit neutrophils injured...
Abstract Collagen remodeling contributes to many physiologic and pathologic processes. In primary tumors, the linearization of collagen fibers promotes cancer cell invasion metastasis is indicative poor prognosis. However, it remains unknown whether there are endogenous inhibitors that could be exploited therapeutically. Here, we show controlled by two secreted matricellular proteins with antagonistic functions. Specifically, WISP1 was cells, bound type I (Col I), linearized Col via its...
Cachexia is a systemic wasting syndrome that increases cancer-associated mortality. How cachexia progressively and differentially impacts distinct tissues largely unknown. Here, we find the heart skeletal muscle undergo at early stages are transcriptionally most impacted by cachexia. We also identify general organ-specific transcriptional changes indicate functional derangement even in do not wasting, such as brain. Secreted factors constitute top category of cancer-regulated genes host...
Many targets have been identified in solid tumors for antibody therapy but it is less clear what surface antigens may be most commonly expressed on disseminated tumor cells. Using malignant pleural effusions as a source of cells, we compared panel 35 their cancer specificity, antigen abundance and functional significance. These previously implicated metastasis fall into four categories: (i) stem cell, (ii) epithelial-mesenchymal transition, (iii) metastatic signature vivo selection (iv)...
Abstract During metastasis, host cells are recruited to disseminated tumor form dynamic, specialized microenvironments (niches) that promote metastatic progression. Platelets interact with during their transit through the circulation and key components of early niches, which formed when initially arrest in distant organs. Interestingly, high platelet counts frequently associated poor outcome disease progression patients solid tumors. Coincident these clinical observations, platelets have...