Cited by 400Cancer Cells and MetastasisMechanisms of cancer metastasisBreast Cancer Treatment Studies

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Lung metastasis genes couple breast tumor size and metastatic spread

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Minn, Andy J., Gupta, Gaorav P., Padua, David, Bos, Paula, Nguyen, Don X., Nuyten, Dimitry, Kreike, Bas, Zhang, Yi, Wang, Yixin, Ishwaran, Hemant, Foekens, John A., van de Vijver, Marc, Massagué, Joan·2007·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0701138104PMC PMC1871856

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Abstract

The association between large tumor size and metastatic risk in a majority of clinical cancers has led to questions as to whether these observations are causally related or whether one is simply a marker for the other. This is partly due to an uncertainty about how metastasis-promoting gene expression changes can arise in primary tumors. We investigated this question through the analysis of a previously defined “lung metastasis gene-expression signature” (LMS) that mediates experimental breast cancer metastasis selectively to the lung and is expressed by primary human breast cancer with a high risk for developing lung metastasis. Experimentally, we demonstrate that the LMS promotes primary tumor growth that enriches for LMS + cells, and it allows for intravasation after reaching a critical tumor size. Clinically, this corresponds to LMS + tumors being larger at diagnosis compared with LMS − tumors and to a marked rise in the incidence of metastasis after LMS + tumors reach 2 cm. Patients with LMS-expressing primary tumors selectively fail in the lung compared with the bone or other visceral sites and have a worse overall survival. The mechanistic linkage between metastasis gene expression, accelerated tumor growth, and likelihood of metastatic recurrence provided by the LMS may help to explain observations of prognostic gene signatures in primary cancer and how tumor growth can both lead to metastasis and be a marker for cells destined to metastasize.

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Authors: Minn, A. J., Gupta, G. P., Padua, D., Bos, P., Nguyen, D. X., Nuyten, D., Kreike, B., Zhang, Y., Wang, Y., Ishwaran, H., Foekens, J. A., van de Vijver, M., & Massagué, J.
Affiliations: University of Chicago (US)
Memorial Sloan Kettering Cancer Center (US)
The Netherlands Cancer Institute (NL)
Johnson & Johnson (United States) (US)
Cleveland Clinic (US)
Erasmus MC (NL)
**Department of Diagnostic Oncology, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands;
ORCID: Minn, Andy J.
Gupta, Gaorav P.
Padua, David
Bos, Paula
Nguyen, Don X.
Kreike, Bas
Zhang, Yi
Wang, Yixin
Ishwaran, Hemant
Massagué, Joan
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2007-04-17
Volume: 104
Issue: 16
Pages: 6740-6745
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0701138104
PMC: PMC1871856
OpenAlex: W2021880490
Cited by: 400
References: 27
Citations by year: 2026: 5 · 2025: 10 · 2024: 3 · 2023: 25 · 2022: 10 · 2021: 32 · 2020: 16 · 2019: 12 · 2018: 19 · 2017: 16 · 2016: 22 · 2015: 22 · 2014: 29 · 2013: 24 · 2012: 28
FWCI: 14.46
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Pure Amsterdam UMC (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Funders: U.S. Public Health Service (P01-94060)
Topics: Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Keywords: breast cancer, lung metastasis, tumor size, primary tumor growth, intravasation, prognostic gene signature, distant recurrence, overall survival, tumor microenvironment
MeSH terms: Animals, Breast Neoplasms, Female, Humans, Lung Neoplasms, Mammary Neoplasms, Experimental, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, Mice

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Lung metastasis genes couple breast tumor size and metastatic spread

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