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Article ; Online: Isaiah Joshua ('Josh') Fidler 1936-2020.

Kalluri, Raghu

Nature cancer

2020 Volume 1, Issue 6, Page(s) 573–574

Language	English
Publishing date	2020-04-13
Publishing country	England
Document type	Journal Article
ISSN	2662-1347
ISSN (online)	2662-1347
DOI	10.1038/s43018-020-0084-9
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Article ; Online: Mouse Models to Evaluate the Functional Role of the Tumor Microenvironment in Cancer Progression and Therapy Responses.

McAndrews, Kathleen M / Mahadevan, Krishnan K / Kalluri, Raghu

Cold Spring Harbor perspectives in medicine

2024

Abstract: The tumor microenvironment (TME) is a complex ecosystem of both cellular and noncellular components that functions to impact the evolution of cancer. Various aspects of the TME have been targeted for the control of cancer; however, TME composition is ... ...

Abstract	The tumor microenvironment (TME) is a complex ecosystem of both cellular and noncellular components that functions to impact the evolution of cancer. Various aspects of the TME have been targeted for the control of cancer; however, TME composition is dynamic, with the overall abundance of immune cells, endothelial cells (ECs), fibroblasts, and extracellular matrix (ECM) as well as subsets of TME components changing at different stages of progression and in response to therapy. To effectively treat cancer, an understanding of the functional role of the TME is needed. Genetically engineered mouse models have enabled comprehensive insight into the complex interactions within the TME ecosystem that regulate disease progression. Here, we review recent advances in mouse models that have been employed to understand how the TME regulates cancer initiation, progression, metastasis, and response to therapy.
Language	English
Publishing date	2024-01-08
Publishing country	United States
Document type	Journal Article
ISSN	2157-1422
ISSN (online)	2157-1422
DOI	10.1101/cshperspect.a041411
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Article ; Online: A novel machine learning algorithm selects proteome signature to specifically identify cancer exosomes.

Li, Bingrui / Kugeratski, Fernanda G / Kalluri, Raghu

eLife

2024 Volume 12

Abstract: Non-invasive early cancer diagnosis remains challenging due to the low sensitivity and specificity of current diagnostic approaches. Exosomes are membrane-bound nanovesicles secreted by all cells that contain DNA, RNA, and proteins that are ... ...

Abstract	Non-invasive early cancer diagnosis remains challenging due to the low sensitivity and specificity of current diagnostic approaches. Exosomes are membrane-bound nanovesicles secreted by all cells that contain DNA, RNA, and proteins that are representative of the parent cells. This property, along with the abundance of exosomes in biological fluids makes them compelling candidates as biomarkers. However, a rapid and flexible exosome-based diagnostic method to distinguish human cancers across cancer types in diverse biological fluids is yet to be defined. Here, we describe a novel machine learning-based computational method to distinguish cancers using a panel of proteins associated with exosomes. Employing datasets of exosome proteins from human cell lines, tissue, plasma, serum, and urine samples from a variety of cancers, we identify Clathrin Heavy Chain (CLTC), Ezrin, (EZR), Talin-1 (TLN1), Adenylyl cyclase-associated protein 1 (CAP1), and Moesin (MSN) as highly abundant universal biomarkers for exosomes and define three panels of pan-cancer exosome proteins that distinguish cancer exosomes from other exosomes and aid in classifying cancer subtypes employing random forest models. All the models using proteins from plasma, serum, or urine-derived exosomes yield AUROC scores higher than 0.91 and demonstrate superior performance compared to Support Vector Machine, K Nearest Neighbor Classifier and Gaussian Naive Bayes. This study provides a reliable protein biomarker signature associated with cancer exosomes with scalable machine learning capability for a sensitive and specific non-invasive method of cancer diagnosis.
MeSH term(s)	Humans ; Proteome/metabolism ; Exosomes/metabolism ; Bayes Theorem ; Neoplasms/diagnosis ; Neoplasms/metabolism ; Biomarkers/metabolism ; Machine Learning ; Algorithms ; Biomarkers, Tumor/genetics
Chemical Substances	Proteome ; Biomarkers ; Biomarkers, Tumor
Language	English
Publishing date	2024-03-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.90390
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Article ; Online: The role of extracellular vesicles in cancer.

Kalluri, Raghu / McAndrews, Kathleen M

Cell

2023 Volume 186, Issue 8, Page(s) 1610–1626

Abstract: Intercellular communication is a key feature of cancer progression and metastasis. Extracellular vesicles (EVs) are generated by all cells, including cancer cells, and recent studies have identified EVs as key mediators of cell-cell communication via ... ...

Abstract	Intercellular communication is a key feature of cancer progression and metastasis. Extracellular vesicles (EVs) are generated by all cells, including cancer cells, and recent studies have identified EVs as key mediators of cell-cell communication via packaging and transfer of bioactive constituents to impact the biology and function of cancer cells and cells of the tumor microenvironment. Here, we review recent advances in understanding the functional contribution of EVs to cancer progression and metastasis, as cancer biomarkers, and the development of cancer therapeutics.
MeSH term(s)	Humans ; Neoplasms/pathology ; Extracellular Vesicles ; Cell Communication/physiology ; Biomarkers, Tumor ; Tumor Microenvironment/physiology
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2023-04-13
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2023.03.010
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Zs.MG 58: Show issues

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Article: A novel machine learning algorithm selects proteome signature to specifically identify cancer exosomes.

Li, Bingrui / Kugeratski, Fernanda G / Kalluri, Raghu

bioRxiv : the preprint server for biology

2023

Abstract	Non-invasive early cancer diagnosis remains challenging due to the low sensitivity and specificity of current diagnostic approaches. Exosomes are membrane-bound nanovesicles secreted by all cells that contain DNA, RNA, and proteins that are representative of the parent cells. This property, along with the abundance of exosomes in biological fluids makes them compelling candidates as biomarkers. However, a rapid and flexible exosome-based diagnostic method to distinguish human cancers across cancer types in diverse biological fluids is yet to be defined. Here, we describe a novel machine learning-based computational method to distinguish cancers using a panel of proteins associated with exosomes. Employing datasets of exosome proteins from human cell lines, tissue, plasma, serum and urine samples from a variety of cancers, we identify Clathrin Heavy Chain (CLTC), Ezrin, (EZR), Talin-1 (TLN1), Adenylyl cyclase-associated protein 1 (CAP1) and Moesin (MSN) as highly abundant universal biomarkers for exosomes and define three panels of pan-cancer exosome proteins that distinguish cancer exosomes from other exosomes and aid in classifying cancer subtypes employing random forest models. All the models using proteins from plasma, serum, or urine-derived exosomes yield AUROC scores higher than 0.91 and demonstrate superior performance compared to Support Vector Machine, K Nearest Neighbor Classifier and Gaussian Naive Bayes. This study provides a reliable protein biomarker signature associated with cancer exosomes with scalable machine learning capability for a sensitive and specific non-invasive method of cancer diagnosis.
Language	English
Publishing date	2023-12-20
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.07.18.549557
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Article ; Online: The biology and function of exosomes in cancer.

Kalluri, Raghu

The Journal of clinical investigation

2016 Volume 126, Issue 4, Page(s) 1208–1215

Abstract: Humans circulate quadrillions of exosomes at all times. Exosomes are a class of extracellular vesicles released by all cells, with a size range of 40-150 nm and a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes likely remove ... ...

Abstract	Humans circulate quadrillions of exosomes at all times. Exosomes are a class of extracellular vesicles released by all cells, with a size range of 40-150 nm and a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes likely remove excess and/or unnecessary constituents from the cells, functioning like garbage bags, although their precise physiological role remains unknown. Additionally, exosomes may mediate specific cell-to-cell communication and activate signaling pathways in cells they fuse or interact with. Exosomes are detected in the tumor microenvironment, and emerging evidence suggests that they play a role in facilitating tumorigenesis by regulating angiogenesis, immunity, and metastasis. Circulating exosomes can be used as liquid biopsies and noninvasive biomarkers for early detection, diagnosis, and treatment of cancer patients.
MeSH term(s)	Animals ; Biomarkers, Tumor/metabolism ; Cell Communication ; Cell-Derived Microparticles ; DNA, Neoplasm/metabolism ; Exosomes/metabolism ; Exosomes/pathology ; Humans ; Neoplasms/diagnosis ; Neoplasms/metabolism ; Neoplasms/pathology ; RNA, Neoplasm/metabolism ; Signal Transduction
Chemical Substances	Biomarkers, Tumor ; DNA, Neoplasm ; RNA, Neoplasm
Language	English
Publishing date	2016-04-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI81135
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Article ; Online: The biology and function of fibroblasts in cancer.

Kalluri, Raghu

Nature reviews. Cancer

2016 Volume 16, Issue 9, Page(s) 582–598

Abstract: Among all cells, fibroblasts could be considered the cockroaches of the human body. They survive severe stress that is usually lethal to all other cells, and they are the only normal cell type that can be live-cultured from post-mortem and decaying ... ...

Abstract	Among all cells, fibroblasts could be considered the cockroaches of the human body. They survive severe stress that is usually lethal to all other cells, and they are the only normal cell type that can be live-cultured from post-mortem and decaying tissue. Their resilient adaptation may reside in their intrinsic survival programmes and cellular plasticity. Cancer is associated with fibroblasts at all stages of disease progression, including metastasis, and they are a considerable component of the general host response to tissue damage caused by cancer cells. Cancer-associated fibroblasts (CAFs) become synthetic machines that produce many different tumour components. CAFs have a role in creating extracellular matrix (ECM) structure and metabolic and immune reprogramming of the tumour microenvironment with an impact on adaptive resistance to chemotherapy. The pleiotropic actions of CAFs on tumour cells are probably reflective of them being a heterogeneous and plastic population with context-dependent influence on cancer.
MeSH term(s)	Cell Differentiation ; Cell Lineage ; Cytokines/secretion ; Disease Progression ; Drug Resistance, Neoplasm/physiology ; Epigenesis, Genetic ; Extracellular Matrix/physiology ; Fibroblasts/physiology ; Fibrosis ; Forecasting ; Humans ; Mesenchymal Stromal Cells/cytology ; Neoplasm Metastasis ; Neoplasm Proteins/physiology ; Neoplasms/blood supply ; Neoplasms/immunology ; Neoplasms/pathology ; Neovascularization, Pathologic/physiopathology ; Stromal Cells/physiology ; Tumor Microenvironment ; Wound Healing
Chemical Substances	Cytokines ; Neoplasm Proteins
Language	English
Publishing date	2016--23
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2062767-1
ISSN	1474-1768 ; 1474-175X
ISSN (online)	1474-1768
ISSN	1474-175X
DOI	10.1038/nrc.2016.73
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Zs.A 5563: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 24: Show issues

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Article ; Online: Emerging role of bacterial extracellular vesicles in cancer.

Chronopoulos, Antonios / Kalluri, Raghu

Oncogene

2020 Volume 39, Issue 46, Page(s) 6951–6960

Abstract: Shedding of microbial extracellular vesicles constitutes a universal mechanism for inter-kingdom and intra-kingdom communication that is conserved among prokaryotic and eukaryotic microbes. In this review we delineate fundamental aspects of bacterial ... ...

Abstract	Shedding of microbial extracellular vesicles constitutes a universal mechanism for inter-kingdom and intra-kingdom communication that is conserved among prokaryotic and eukaryotic microbes. In this review we delineate fundamental aspects of bacterial extracellular vesicles (BEVs) including their biogenesis, cargo composition, and interactions with host cells. We critically examine the evidence that BEVs from the host gut microbiome can enter the circulatory system to disseminate to distant organs and tissues. The potential involvement of BEVs in carcinogenesis is evaluated and future research ideas explored. We further discuss the potential of BEVs in microbiome-based liquid biopsies for cancer diagnostics and bioengineering strategies for cancer therapy.
MeSH term(s)	Cell Communication/physiology ; Cell Engineering ; Cell- and Tissue-Based Therapy/methods ; Extracellular Vesicles/metabolism ; Gastrointestinal Microbiome/physiology ; Host Microbial Interactions/physiology ; Humans ; Liquid Biopsy/methods ; Neoplasm Metastasis/pathology ; Neoplasms/diagnosis ; Neoplasms/microbiology ; Neoplasms/pathology ; Neoplasms/therapy
Keywords	covid19
Language	English
Publishing date	2020-10-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/s41388-020-01509-3
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Zs.A 2218: Show issues

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Article ; Online: Biology and therapeutic potential of mesenchymal stem cell-derived exosomes.

Xunian, Zhou / Kalluri, Raghu

Cancer science

2020 Volume 111, Issue 9, Page(s) 3100–3110

Abstract: Mesenchymal stem cells (MSC) are multipotent stromal cells with the potential to differentiate into several cell types. MSC-based therapy has emerged as a promising strategy for various diseases. Accumulating evidence suggests that the paracrine effects ... ...

Abstract	Mesenchymal stem cells (MSC) are multipotent stromal cells with the potential to differentiate into several cell types. MSC-based therapy has emerged as a promising strategy for various diseases. Accumulating evidence suggests that the paracrine effects of MSC are partially exerted by the secretion of soluble factors, in particular exosomes. MSC-derived exosomes are involved in intercellular communication through transfer of proteins, RNA, DNA and bioactive lipids, which might constitute a novel intercellular communication mode. This review illustrates the current knowledge on the composition and biological functions as well as the therapeutic potential of MSC-derived exosomes in cancer, with a focus on clinical translation opportunities.
MeSH term(s)	Animals ; Biological Products/therapeutic use ; Cell Communication ; Cell-Derived Microparticles/metabolism ; Cellular Microenvironment ; Clinical Trials as Topic ; Drug Delivery Systems ; Exosomes/metabolism ; Humans ; Immunomodulation ; Mesenchymal Stem Cells/metabolism
Chemical Substances	Biological Products
Language	English
Publishing date	2020-07-28
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2115647-5
ISSN	1349-7006 ; 1347-9032
ISSN (online)	1349-7006
ISSN	1347-9032
DOI	10.1111/cas.14563
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Article ; Online: Exosomes as mediators of immune regulation and immunotherapy in cancer.

Kugeratski, Fernanda G / Kalluri, Raghu

The FEBS journal

2020 Volume 288, Issue 1, Page(s) 10–35

Abstract: Exosomes are nanosized extracellular vesicles of endosomal origin that enclose a multitude of functional biomolecules. Exosomes have emerged as key players of intercellular communication in physiological and pathological conditions. In cancer, depending ... ...

Abstract	Exosomes are nanosized extracellular vesicles of endosomal origin that enclose a multitude of functional biomolecules. Exosomes have emerged as key players of intercellular communication in physiological and pathological conditions. In cancer, depending on the context, exosomes can oppose or potentiate the development of an aggressive tumor microenvironment, thereby impacting tumor progression and clinical outcome. Increasing evidence has established exosomes as important mediators of immune regulation in cancer, as they deliver a plethora of signals that can either support or restrain immunosuppression of lymphoid and myeloid cell populations in tumors. Here, we review the current knowledge related to exosome-mediated regulation of lymphoid (T lymphocytes, B lymphocytes, and NK cells) and myeloid (macrophages, dendritic cells, monocytes, myeloid-derived suppressor cells, and neutrophils) cell populations in cancer. We also discuss the translational potential of engineered exosomes as immunomodulatory agents for cancer therapy.
MeSH term(s)	B-Lymphocytes/drug effects ; B-Lymphocytes/immunology ; B-Lymphocytes/pathology ; B7-H1 Antigen/genetics ; B7-H1 Antigen/immunology ; B7-H1 Antigen/pharmacology ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Dendritic Cells/pathology ; Exosomes/immunology ; Exosomes/metabolism ; Exosomes/transplantation ; Fas Ligand Protein/genetics ; Fas Ligand Protein/immunology ; Fas Ligand Protein/pharmacology ; Gene Expression ; Humans ; Immunomodulation ; Immunotherapy/methods ; Killer Cells, Natural/drug effects ; Killer Cells, Natural/immunology ; Killer Cells, Natural/pathology ; Macrophages/drug effects ; Macrophages/immunology ; Macrophages/pathology ; Monocytes/drug effects ; Monocytes/immunology ; Monocytes/pathology ; Myeloid-Derived Suppressor Cells/drug effects ; Myeloid-Derived Suppressor Cells/immunology ; Myeloid-Derived Suppressor Cells/pathology ; Neoplasms/genetics ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplasms/therapy ; Neutrophils/drug effects ; Neutrophils/immunology ; Neutrophils/pathology ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; T-Lymphocytes/pathology ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/genetics ; Tumor Microenvironment/immunology
Chemical Substances	B7-H1 Antigen ; CD274 protein, human ; FASLG protein, human ; Fas Ligand Protein
Language	English
Publishing date	2020-10-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.15558
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