LIVIVO - Search results -

Search results

Result 1 - 10 of total 20

Search options

Article ; Online: Integrating integrins with the hallmarks of cancer.

Haake, Scott M / Rios, Brenda L / Pozzi, Ambra / Zent, Roy

Matrix biology : journal of the International Society for Matrix Biology

2024

Abstract: Epithelial cells adhere to a specialized extracellular matrix called the basement membrane which allows them to polarize and form epithelial tissues. The extracellular matrix provides essential physical scaffolding and biochemical and biophysical cues ... ...

Abstract	Epithelial cells adhere to a specialized extracellular matrix called the basement membrane which allows them to polarize and form epithelial tissues. The extracellular matrix provides essential physical scaffolding and biochemical and biophysical cues required for tissue morphogenesis, differentiation, function, and homeostasis. Epithelial cell adhesion to the extracellular matrix (i.e., basement membrane) plays a critical role in organizing epithelial tissues, separating the epithelial cells from the stroma. Epithelial cell detachment from the basement membrane classically results in death, though detachment or invasion through the basement membrane represents a critical step in carcinogenesis. Epithelial cells bind to the extracellular matrix via specialized matrix receptors, including integrins. Integrins are transmembrane receptors that form a mechanical linkage between the extracellular matrix and the intracellular cytoskeleton and are required for anchorage-dependent cellular functions such as proliferation, migration, and invasion. The role of integrins in the development, growth, and dissemination of multiple types of carcinomas has been investigated by numerous methodologies, which has led to great complexity. To organize this vast array of information, we have utilized the "Hallmarks of Cancer" from Hanahan and Weinberg as a convenient framework to discuss the role of integrins in the pathogenesis of cancers. This review explores this biology and how its complexity has impacted the development of integrin-targeted anti-cancer therapeutics.
Language	English
Publishing date	2024-04-25
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1183793-7
ISSN	1569-1802 ; 0945-053X
ISSN (online)	1569-1802
ISSN	0945-053X
DOI	10.1016/j.matbio.2024.04.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1694: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Article ; Online: Hypoxia-induced epithelial to mesenchymal transition in cancer.

Hapke, Robert Y / Haake, Scott M

Cancer letters

2020 Volume 487, Page(s) 10–20

Abstract: A common feature of many solid tumors is low oxygen conditions due to inadequate blood supply. Hypoxia induces hypoxia inducible factor (HIF) stabilization and downstream signaling. This signaling has pleiotropic roles in cancers, including the promotion ...

Abstract	A common feature of many solid tumors is low oxygen conditions due to inadequate blood supply. Hypoxia induces hypoxia inducible factor (HIF) stabilization and downstream signaling. This signaling has pleiotropic roles in cancers, including the promotion of cellular proliferation, changes in metabolism, and induction of angiogenesis. In addition, hypoxia is becoming recognized as an important driver of epithelial-to-mesenchymal (EMT) in cancer. During EMT, epithelial cells lose their typical polarized states and transition to a more mobile mesenchymal phenotype. Hypoxia induces this transition by modulating EMT signaling pathways, inducing EMT transcription factor activity, and regulating miRNA networks. As both hypoxia and EMT modulate the tumor microenvironment (TME) and are associated with immunosuppression, we also explore how these pathways may impact response to immuno-oncology therapeutics.
MeSH term(s)	Cell Line, Tumor ; Cell Proliferation/genetics ; Epithelial-Mesenchymal Transition/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Neoplasms/genetics ; Neoplasms/pathology ; Signal Transduction ; Tumor Hypoxia/genetics ; Tumor Microenvironment/genetics
Language	English
Publishing date	2020-05-26
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2020.05.012
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1177: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Renal cancer subtypes: Should we be lumping or splitting for therapeutic decision making?

Haake, Scott M / Rathmell, W Kimryn

Cancer

2017 Volume 123, Issue 2, Page(s) 200–209

Abstract: The treatment of advanced renal cell carcinoma has posed a challenge for decades, in part because of common themes related to intrinsic resistance to cytotoxic chemotherapy and the obscure biology of these cancer types. Forward movement in the treatment ... ...

Abstract	The treatment of advanced renal cell carcinoma has posed a challenge for decades, in part because of common themes related to intrinsic resistance to cytotoxic chemotherapy and the obscure biology of these cancer types. Forward movement in the treatment of the renal cell carcinomas thus can be approached in 2 ways: by splitting the tumor types along histologic and molecular features, in the hopes of coupling highly precision-focused therapy on a subset of patients who have disease with the most potential for benefit; or by lumping the various biologies and histologies together, to include the rarer renal cell carcinoma types with the more common types. The former strategy satisfies the desire for customized precision in treatment delivery, whereas the latter strategy allows clinicians to offer a wider therapeutic menu in a set of diseases we are continuing to learn about on a physiologic and molecular level. Cancer 2017;123:200-209. © 2016 American Cancer Society.
MeSH term(s)	Carcinoma, Renal Cell/drug therapy ; Carcinoma, Renal Cell/pathology ; Decision Making/physiology ; Humans ; Kidney Neoplasms/drug therapy ; Kidney Neoplasms/pathology
Language	English
Publishing date	2017-01-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.30314
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Uh III Zs.146: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: SETD2 regulates the methylation of translation elongation factor eEF1A1 in clear cell renal cell carcinoma.

Hapke, Robert / Venton, Lindsay / Rose, Kristie Lindsay / Sheng, Quanhu / Reddy, Anupama / Prather, Rebecca / Jones, Angela / Rathmell, W Kimryn / Haake, Scott M

Kidney cancer journal : official journal of the Kidney Cancer Association

2022 Volume 6, Issue 3, Page(s) 179–193

Abstract: Background: SET domain-containing protein 2 (: Objective: Initially, we sought to explore SETD2-dependent changes in lysine methylation of proteins in proximal renal tubule cells. Subsequently, we focused on changes in lysine methylation of the ... ...

Abstract	Background: SET domain-containing protein 2 ( Objective: Initially, we sought to explore SETD2-dependent changes in lysine methylation of proteins in proximal renal tubule cells. Subsequently, we focused on changes in lysine methylation of the translation elongation factor eEF1A1. Methods: To accomplish these objectives, we initially performed a systems-wide analysis of protein lysine-methylation and expression in wild type (WT) and Results: We observed decreased lysine methylation of the translation elongation factor eEF1A1. Conclusion: Overall, these data suggest that
Language	English
Publishing date	2022-11-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2244563-8
ISSN	1933-0871 ; 1933-0863
ISSN (online)	1933-0871
ISSN	1933-0863
DOI	10.3233/kca-220009
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Insights into the Genetic Basis of the Renal Cell Carcinomas from The Cancer Genome Atlas.

Haake, Scott M / Weyandt, Jamie D / Rathmell, W Kimryn

Molecular cancer research : MCR

2016 Volume 14, Issue 7, Page(s) 589–598

Abstract: The renal cell carcinomas (RCC), clear cell, papillary, and chromophobe, have recently undergone an unmatched genomic characterization by The Cancer Genome Atlas. This analysis has revealed new insights into each of these malignancies and underscores the ...

Abstract	The renal cell carcinomas (RCC), clear cell, papillary, and chromophobe, have recently undergone an unmatched genomic characterization by The Cancer Genome Atlas. This analysis has revealed new insights into each of these malignancies and underscores the unique biology of clear cell, papillary, and chromophobe RCC. Themes that have emerged include distinct mechanisms of metabolic dysregulation and common mutations in chromatin modifier genes. Importantly, the papillary RCC classification encompasses a heterogeneous group of diseases, each with highly distinct genetic and molecular features. In conclusion, this review summarizes RCCs that represent a diverse set of malignancies, each with novel biologic programs that define new paradigms for cancer biology. Mol Cancer Res; 14(7); 589-98. ©2016 AACR.
MeSH term(s)	Animals ; Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/pathology ; Genome ; Humans ; Kidney Neoplasms/genetics ; Kidney Neoplasms/pathology
Language	English
Publishing date	2016-06-21
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2098788-2
ISSN	1557-3125 ; 1541-7786
ISSN (online)	1557-3125
ISSN	1541-7786
DOI	10.1158/1541-7786.MCR-16-0115
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5744: 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)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: VHL loss reprograms the immune landscape to promote an inflammatory myeloid microenvironment in renal tumorigenesis.

The Journal of clinical investigation

2024 Volume 134, Issue 8

Abstract: Clear cell renal cell carcinoma (ccRCC) is characterized by dysregulated hypoxia signaling and a tumor microenvironment (TME) highly enriched in myeloid and lymphoid cells. Loss of the von Hippel Lindau (VHL) gene is a critical early event in ccRCC ... ...

Abstract	Clear cell renal cell carcinoma (ccRCC) is characterized by dysregulated hypoxia signaling and a tumor microenvironment (TME) highly enriched in myeloid and lymphoid cells. Loss of the von Hippel Lindau (VHL) gene is a critical early event in ccRCC pathogenesis and promotes stabilization of HIF. Whether VHL loss in cancer cells affects immune cells in the TME remains unclear. Using Vhl WT and Vhl-KO in vivo murine kidney cancer Renca models, we found that Vhl-KO tumors were more infiltrated by immune cells. Tumor-associated macrophages (TAMs) from Vhl-deficient tumors demonstrated enhanced in vivo glucose consumption, phagocytosis, and inflammatory transcriptional signatures, whereas lymphocytes from Vhl-KO tumors showed reduced activation and a lower response to anti-programmed cell death 1 (anti-PD-1) therapy in vivo. The chemokine CX3CL1 was highly expressed in human ccRCC tumors and was associated with Vhl deficiency. Deletion of Cx3cl1 in cancer cells decreased myeloid cell infiltration associated with Vhl loss to provide a mechanism by which Vhl loss may have contributed to the altered immune landscape. Here, we identify cancer cell-specific genetic features that drove environmental reprogramming and shaped the tumor immune landscape, with therapeutic implications for the treatment of ccRCC.
MeSH term(s)	Animals ; Humans ; Mice ; Carcinogenesis/genetics ; Carcinoma, Renal Cell/genetics ; Cell Transformation, Neoplastic ; Kidney ; Kidney Neoplasms/genetics ; Tumor Microenvironment ; Von Hippel-Lindau Tumor Suppressor Protein/genetics
Chemical Substances	VHL protein, human (EC 6.3.2.-) ; VHL protein, mouse (EC 6.3.2.-) ; Von Hippel-Lindau Tumor Suppressor Protein (EC 2.3.2.27)
Language	English
Publishing date	2024-04-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI173934
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ua VI Zs.184: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Strategies to overcome therapeutic resistance in renal cell carcinoma.

Siska, Peter J / Beckermann, Kathryn E / Rathmell, W Kimryn / Haake, Scott M

Urologic oncology

2017 Volume 35, Issue 3, Page(s) 102–110

Abstract: Background: Renal cell cancer (RCC) is a prevalent and lethal disease. At time of diagnosis, most patients present with localized disease. For these patients, the standard of care includes nephrectomy with close monitoring thereafter. While many ... ...

Abstract	Background: Renal cell cancer (RCC) is a prevalent and lethal disease. At time of diagnosis, most patients present with localized disease. For these patients, the standard of care includes nephrectomy with close monitoring thereafter. While many patients will be cured, 5-year recurrence rates range from 30% to 60%. Furthermore, nearly one-third of patients present with metastatic disease at time of diagnosis. Metastatic disease is rarely curable and typically lethal. Cytotoxic chemotherapy and radiation alone are incapable of controlling the disease. Extensive effort was expended in the development of cytokine therapies but response rates remain low. Newer agents targeting angiogenesis and mTOR signaling emerged in the 2000s and revolutionized patient care. While these agents improve progression free survival, the development of resistance is nearly universal. A new era of immunotherapy is now emerging, led by the checkpoint inhibitors. However, therapeutic resistance remains a complex issue that is likely to persist. Methods and purpose: In this review, we systematically evaluate preclinical research and clinical trials that address resistance to the primary RCC therapies, including anti-angiogenesis agents, mTOR inhibitors, and immunotherapies. As clear cell RCC is the most common adult kidney cancer and has been the focus of most studies, it will be the focus of this review.
MeSH term(s)	Angiogenesis Inhibitors/pharmacology ; Angiogenesis Inhibitors/therapeutic use ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Carcinoma, Renal Cell/immunology ; Carcinoma, Renal Cell/mortality ; Carcinoma, Renal Cell/pathology ; Carcinoma, Renal Cell/therapy ; Clinical Trials as Topic ; Costimulatory and Inhibitory T-Cell Receptors/antagonists & inhibitors ; Cytotoxicity, Immunologic/drug effects ; Disease Progression ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Humans ; Immunotherapy/methods ; Kidney/blood supply ; Kidney/pathology ; Kidney Neoplasms/immunology ; Kidney Neoplasms/mortality ; Kidney Neoplasms/pathology ; Kidney Neoplasms/therapy ; Neoplasm Recurrence, Local/immunology ; Neoplasm Recurrence, Local/mortality ; Neoplasm Recurrence, Local/pathology ; Neoplasm Recurrence, Local/therapy ; Neovascularization, Pathologic/drug therapy ; Neovascularization, Pathologic/pathology ; Nephrectomy ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Receptors, Vascular Endothelial Growth Factor/metabolism ; Signal Transduction/drug effects ; TOR Serine-Threonine Kinases/metabolism
Chemical Substances	Angiogenesis Inhibitors ; Antineoplastic Agents ; Costimulatory and Inhibitory T-Cell Receptors ; Protein Kinase Inhibitors ; MTOR protein, human (EC 2.7.1.1) ; Receptors, Vascular Endothelial Growth Factor (EC 2.7.10.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2017-01-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1336505-8
ISSN	1873-2496 ; 1078-1439
ISSN (online)	1873-2496
ISSN	1078-1439
DOI	10.1016/j.urolonc.2016.12.002
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 4817: 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)

Order via subito

Details ▾

Article ; Online: Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages.

Obradovic, Aleksandar / Chowdhury, Nivedita / Haake, Scott M / Ager, Casey / Wang, Vinson / Vlahos, Lukas / Guo, Xinzheng V / Aggen, David H / Rathmell, W Kimryn / Jonasch, Eric / Johnson, Joyce E / Roth, Marc / Beckermann, Kathryn E / Rini, Brian I / McKiernan, James / Califano, Andrea / Drake, Charles G

Cell

2021 Volume 184, Issue 11, Page(s) 2988–3005.e16

Abstract: Clear cell renal carcinoma (ccRCC) is a heterogeneous disease with a variable post-surgical course. To assemble a comprehensive ccRCC tumor microenvironment (TME) atlas, we performed single-cell RNA sequencing (scRNA-seq) of hematopoietic and non- ... ...

Abstract	Clear cell renal carcinoma (ccRCC) is a heterogeneous disease with a variable post-surgical course. To assemble a comprehensive ccRCC tumor microenvironment (TME) atlas, we performed single-cell RNA sequencing (scRNA-seq) of hematopoietic and non-hematopoietic subpopulations from tumor and tumor-adjacent tissue of treatment-naive ccRCC resections. We leveraged the VIPER algorithm to quantitate single-cell protein activity and validated this approach by comparison to flow cytometry. The analysis identified key TME subpopulations, as well as their master regulators and candidate cell-cell interactions, revealing clinically relevant populations, undetectable by gene-expression analysis. Specifically, we uncovered a tumor-specific macrophage subpopulation characterized by upregulation of TREM2/APOE/C1Q, validated by spatially resolved, quantitative multispectral immunofluorescence. In a large clinical validation cohort, these markers were significantly enriched in tumors from patients who recurred following surgery. The study thus identifies TREM2/APOE/C1Q-positive macrophage infiltration as a potential prognostic biomarker for ccRCC recurrence, as well as a candidate therapeutic target.
MeSH term(s)	Adult ; Apolipoproteins E/genetics ; Apolipoproteins E/metabolism ; Biomarkers, Tumor/genetics ; Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/metabolism ; Carcinoma, Renal Cell/pathology ; Cohort Studies ; Female ; Gene Expression/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Kidney/metabolism ; Kidney Neoplasms/pathology ; Lymphocytes, Tumor-Infiltrating/pathology ; Macrophages/metabolism ; Male ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; Middle Aged ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/metabolism ; Prognosis ; Receptors, Complement/genetics ; Receptors, Complement/metabolism ; Receptors, Immunologic/genetics ; Receptors, Immunologic/metabolism ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods ; Tumor Microenvironment ; Tumor-Associated Macrophages/metabolism ; Tumor-Associated Macrophages/physiology
Chemical Substances	ApoE protein, human ; Apolipoproteins E ; Biomarkers, Tumor ; Membrane Glycoproteins ; Receptors, Complement ; Receptors, Immunologic ; TREM2 protein, human ; complement 1q receptor
Language	English
Publishing date	2021-05-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2021.04.038
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 58: Show issues

Order via subito

Details ▾

Article ; Online: Ligand-independent integrin β1 signaling supports lung adenocarcinoma development.

JCI insight

2022 Volume 7, Issue 15

Abstract: Integrins - the principal extracellular matrix (ECM) receptors of the cell - promote cell adhesion, migration, and proliferation, which are key events for cancer growth and metastasis. To date, most integrin-targeted cancer therapeutics have disrupted ... ...

Abstract	Integrins - the principal extracellular matrix (ECM) receptors of the cell - promote cell adhesion, migration, and proliferation, which are key events for cancer growth and metastasis. To date, most integrin-targeted cancer therapeutics have disrupted integrin-ECM interactions, which are viewed as critical for integrin functions. However, such agents have failed to improve cancer patient outcomes. We show that the highly expressed integrin β1 subunit is required for lung adenocarcinoma development in a carcinogen-induced mouse model. Likewise, human lung adenocarcinoma cell lines with integrin β1 deletion failed to form colonies in soft agar and tumors in mice. Mechanistically, we demonstrate that these effects do not require integrin β1-mediated adhesion to ECM but are dependent on integrin β1 cytoplasmic tail-mediated activation of focal adhesion kinase (FAK). These studies support a critical role for integrin β1 in lung tumorigenesis that is mediated through constitutive, ECM binding-independent signaling involving the cytoplasmic tail.
MeSH term(s)	Adenocarcinoma/genetics ; Adenocarcinoma of Lung/genetics ; Animals ; Humans ; Integrin beta1/genetics ; Integrin beta1/metabolism ; Integrins ; Ligands ; Lung Neoplasms/pathology ; Mice
Chemical Substances	Integrin beta1 ; Integrins ; Ligands
Language	English
Publishing date	2022-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.154098
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages

Obradovic, Aleksandar / Chowdhury, Nivedita / Haake, Scott M / Ager, Casey / Wang, Vinson / Vlahos, Lukas / Guo, Xinzheng V / Aggen, David H / Rathmell, W. Kimryn / Jonasch, Eric / Johnson, Joyce E / Roth, Marc / Beckermann, Kathryn E / Rini, Brian I / McKiernan, James / Califano, Andrea / Drake, Charles G

Cell. 2021 May 27, v. 184, no. 11

2021

Abstract	Clear cell renal carcinoma (ccRCC) is a heterogeneous disease with a variable post-surgical course. To assemble a comprehensive ccRCC tumor microenvironment (TME) atlas, we performed single-cell RNA sequencing (scRNA-seq) of hematopoietic and non-hematopoietic subpopulations from tumor and tumor-adjacent tissue of treatment-naive ccRCC resections. We leveraged the VIPER algorithm to quantitate single-cell protein activity and validated this approach by comparison to flow cytometry. The analysis identified key TME subpopulations, as well as their master regulators and candidate cell-cell interactions, revealing clinically relevant populations, undetectable by gene-expression analysis. Specifically, we uncovered a tumor-specific macrophage subpopulation characterized by upregulation of TREM2/APOE/C1Q, validated by spatially resolved, quantitative multispectral immunofluorescence. In a large clinical validation cohort, these markers were significantly enriched in tumors from patients who recurred following surgery. The study thus identifies TREM2/APOE/C1Q-positive macrophage infiltration as a potential prognostic biomarker for ccRCC recurrence, as well as a candidate therapeutic target.
Keywords	RNA ; algorithms ; biomarkers ; carcinoma ; flow cytometry ; fluorescent antibody technique ; gene expression ; macrophages ; single cell protein ; surgery
Language	English
Dates of publication	2021-0527
Size	p. 2988-3005.e16.
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2021.04.038
Database	NAL-Catalogue (AGRICOLA)

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Bonn / Germany

Z 75/702: Show issues
Z 93: Show issues

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

To top

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED