Determinants of renal cell carcinoma invasion and metastatic competence

Kangsan Kim, Qinbo Zhou, Alana Christie, Christina Stevens, Yuanqing Ma, Oreoluwa Onabolu, Suneetha Chintalapati, Tiffani Mckenzie, Vanina Toffessi Tcheuyap, Layton Woolford, He Zhang, Nirmish Singla, Pravat Kumar Parida, Mauricio Marquez-Palencia, Ivan Pedrosa, Vitaly Margulis, Arthur Sagalowsky, Zhiqun Xie, Tao Wang, Steffen Durinck, Zora Modrusan, Somasekar Seshagiri, Payal Kapur (), James Brugarolas () and Srinivas Malladi ()
Additional contact information
Kangsan Kim: University of Texas Southwestern Medical Center
Qinbo Zhou: University of Texas Southwestern Medical Center
Alana Christie: The University of Texas Southwestern Medical Center
Christina Stevens: The University of Texas Southwestern Medical Center
Yuanqing Ma: The University of Texas Southwestern Medical Center
Oreoluwa Onabolu: The University of Texas Southwestern Medical Center
Suneetha Chintalapati: University of Texas Southwestern Medical Center
Tiffani Mckenzie: The University of Texas Southwestern Medical Center
Vanina Toffessi Tcheuyap: The University of Texas Southwestern Medical Center
Layton Woolford: The University of Texas Southwestern Medical Center
He Zhang: The University of Texas Southwestern Medical Center
Nirmish Singla: The University of Texas Southwestern Medical Center
Pravat Kumar Parida: University of Texas Southwestern Medical Center
Mauricio Marquez-Palencia: University of Texas Southwestern Medical Center
Ivan Pedrosa: The University of Texas Southwestern Medical Center
Vitaly Margulis: The University of Texas Southwestern Medical Center
Arthur Sagalowsky: The University of Texas Southwestern Medical Center
Zhiqun Xie: University of Texas Southwestern Medical Center
Tao Wang: University of Texas Southwestern Medical Center
Steffen Durinck: Genentech, Inc.
Zora Modrusan: Genentech, Inc.
Somasekar Seshagiri: Genentech, Inc.
Payal Kapur: University of Texas Southwestern Medical Center
James Brugarolas: The University of Texas Southwestern Medical Center
Srinivas Malladi: University of Texas Southwestern Medical Center

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Metastasis is the principal cause of cancer related deaths. Tumor invasion is essential for metastatic spread. However, determinants of invasion are poorly understood. We addressed this knowledge gap by leveraging a unique attribute of kidney cancer. Renal tumors invade into large vessels forming tumor thrombi (TT) that migrate extending sometimes into the heart. Over a decade, we prospectively enrolled 83 ethnically-diverse patients undergoing surgical resection for grossly invasive tumors at UT Southwestern Kidney Cancer Program. In this study, we perform comprehensive histological analyses, integrate multi-region genomic studies, generate in vivo models, and execute functional studies to define tumor invasion and metastatic competence. We find that invasion is not always associated with the most aggressive clone. Driven by immediate early genes, invasion appears to be an opportunistic trait attained by subclones with diverse oncogenomic status in geospatial proximity to vasculature. We show that not all invasive tumors metastasize and identify determinants of metastatic competency. TT associated with metastases are characterized by higher grade, mTOR activation and a particular immune contexture. Moreover, TT grade is a better predictor of metastasis than overall tumor grade, which may have implications for clinical practice.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-25918-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25918-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-25918-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().