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Lung metastasis genes couple breast tumor size and metastatic spread
Open accessAbstract
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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“CXCL1 emerged among a set of genes whose expression is associated with lung relapse in breast tumors, including tumors that had not been exposed to prior chemotherapy (Minn et al., 2007; Minn et al., 2005), and as a gene that increases the aggressiveness of circulating breast tumor cells (Kim et al., 2009).”
From A CXCL1 Paracrine Network Links Cancer Chemoresistance and Metastasis (2012) · cites this paper as Minn et al., 2007
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Cites
In silico prediction of protein-protein interactions in human macrophages
Souiai, O., Guerfali, F. Z., Miled, S. B., Brun, C., & Benkahla, A. (2014) · BMC Research Notes · doi:10.1186/1756-0500-7-157 · Cited by 10,785
Significance analysis of microarrays applied to the ionizing radiation response
Tusher, V. G., Tibshirani, R., & Chu, G. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.091062498 · Cited by 10,568
Gene expression profiling predicts clinical outcome of breast cancer
van 't Veer, L. J., Dai, H., van de Vijver, M. J., He, Y. D., Hart, A. A. M., Mao, M., Peterse, H. L., van der Kooy, K., Marton, M. J., Witteveen, A. T., et al. (2002) · Nature · doi:10.1038/415530a · Cited by 9,536
A Gene-Expression Signature as a Predictor of Survival in Breast Cancer
van de Vijver, M. J., He, Y. D., Veer, L. V. ‘., Dai, H. A., Hart, A. A. M., Voskuil, D. W., Schreiber, G. J., Peterse, J. L., Roberts, C., Marton, M. J., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa021967 · Cited by 6,474
A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer
Paik, S., Shak, S., Tang, G., Kim, C., Baker, J. B., Cronin, M. T., Baehner, F. L., Walker, M. G., Watson, D., Park, T., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa041588 · Cited by 6,321
Repeated observation of breast tumor subtypes in independent gene expression data sets
Sørlie, T., Tibshirani, R. J., Parker, J. S., Hastie, T. J., Marron, J. S., Nobel, A. B., Deng, S., Johnsen, H., Pesich, R., Geisler, S. B., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0932692100 · Cited by 5,508
TM4: a free, open-source system for microarray data management and analysis
Saeed, A. I., Sharov, V., White, J., Li, J., Liang, W., Bhagabati, N., Braisted, J., Klapa, M., Currier, T., Thiagarajan, M., et al. (2003) · BioTechniques · doi:10.2144/03342mt01 · Cited by 4,837
The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited
Fidler, I. J. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1098 · Cited by 4,686
Dissemination and growth of cancer cells in metastatic sites
Chambers, A. F., Groom, A. C., & MacDonald, I. C. (2002) · Nature reviews. Cancer · doi:10.1038/nrc865 · Cited by 4,018
Genes that mediate breast cancer metastasis to lung
Minn, A. J., Gupta, G. P., Siegel, P. M., Bos, P. D., Shu, W., Giri, D. D., Viale, A., Olshen, A. B., Gerald, W. L., & Massagué, J. (2005) · Nature · doi:10.1038/nature03799 · Cited by 2,922
Self-citationGene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer
Wang, Y., Klijn, J. G. M., Zhang, Y., Sieuwerts, A. M., Look, M. P., Yang, F., Talantov, D., Timmermans, M. A. M., Gelder, M. E. M., Yu, J. X., et al. (2005) · The Lancet · doi:10.1016/s0140-6736(05)17947-1 · Cited by 2,831
Self-citationA multigenic program mediating breast cancer metastasis to bone
Kang, Y., Siegel, P. M., Shu, W., Drobnjak, M., Käkönen, S.-M., Cordon‐Cardo, C., Guise, T. A., & Massagué, J. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00132-6 · Cited by 2,605
Self-citationA molecular signature of metastasis in primary solid tumors
Ramaswamy, S., Ross, K. N., Lander, E. S., & Golub, T. R. (2002) · Nature Genetics · doi:10.1038/ng1060 · Cited by 2,469
Oncogenic pathway signatures in human cancers as a guide to targeted therapies
Bild, A., Yao, G., Chang, J. T., Wang, Q., Potti, A., Chasse, D. A. D., Joshi, M.-B., Harpole, D. H., Lancaster, J. M., Berchuck, A., et al. (2005) · Nature · doi:10.1038/nature04296 · Cited by 2,008
[9] TM4 Microarray Software Suite
Saeed, A. I., BHAGABATI, N. K., Braisted, J. C., Liang, W. P., Sharov, V., Howe, E., Li, J., Thiagarajan, M., White, J., & Quackenbush, J. F. (2006) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(06)11009-5 · Cited by 1,996
The molecular portraits of breast tumors are conserved across microarray platforms
Hu, Z., Fan, C., Oh, D. S., Marron, J. S., He, X., Qaqish, B. F., Livasy, C., Carey, L., Reynolds, E. R., Dressler, L. G., et al. (2006) · BMC Genomics · doi:10.1186/1471-2164-7-96 · Cited by 1,587
Concordance among Gene-Expression–Based Predictors for Breast Cancer
Fan, C., Oh, D. S., Wessels, L. F. A., Weigelt, B., Nuyten, D. S. A., Nobel, A. B., Veer, L. J. V., & Perou, C. M. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa052933 · Cited by 1,356
Self-citationChang, H. Y., Nuyten, D. S. A., Sneddon, J. B., Hastie, T., Tibshirani, R., Sørlie, T., Dai, H., He, Y. D., van't Veer, L. J., Bartelink, H., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409462102 · Cited by 981
Self-citationMetastasis genes: A progression puzzle
Bernards, R., & Weinberg, R. A. (2002) · Nature · doi:10.1038/418823a · Cited by 801
Mediators of vascular remodelling co-opted for sequential steps in lung metastasis
Gupta, G. P., Nguyen, D. X., Chiang, A. C., Bos, P. D., Kim, J. Y., Nadal, C., Gomis, R. R., Manova-Todorova, K. O., & Massagué, J. (2007) · Nature · doi:10.1038/nature05760 · Cited by 735
Self-citationIs breast cancer survival improving?
Giordano, S. H., Buzdar, A. U., Smith, T. L., Kau, S., Yang, Y., & Hortobágyi, G. N. (2003) · Cancer · doi:10.1002/cncr.11859 · Cited by 542
Koscielny, S., Tubiana, M., Lê, M. G., Valleron, A., Mouriesse, H., Contesso, G., & Sarrazin, D. (1984) · British Journal of Cancer · doi:10.1038/bjc.1984.112 · Cited by 356
Genes Associated With Breast Cancer Metastatic to Bone
Smid, M., Wang, Y., Klijn, J. G. M., Sieuwerts, A. M., Zhang, Y., Atkins, D., Martens, J. W. M., & Foekens, J. A. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.03.8802 · Cited by 325
Self-citationGenetic regulators of large-scale transcriptional signatures in cancer
Adler, A. S., Lin, M., Horlings, H. M., Nuyten, D. S. A., van de Vijver, M. J., & Chang, H. Y. (2006) · Nature Genetics · doi:10.1038/ng1752 · Cited by 232
Self-citationPittman, J. L., Huang, E. S., Dressman, H. K., Horng, C., Cheng, S. H., Tsou, M.-H., Chen, C.-M., Bild, A., Iversen, E. S., Huang, A. T., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401736101 · Cited by 218
Sorting Out Breast-Cancer Gene Signatures
Massagué, J. (2007) · New England Journal of Medicine · doi:10.1056/nejme068292 · Cited by 126
Self-citationClinical Progression of Breast Cancer Malignant Behavior: What to Expect and When to Expect it
Heimann, R., & Hellmän, S. (2000) · Journal of Clinical Oncology · doi:10.1200/jco.2000.18.3.591 · Cited by 106
Research works printed but not linked: 1
- H Ishwaran, UB Kogalur R News, in press. (2007).
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Microenvironmental regulation of metastasis
Joyce, J. A., & Pollard, J. W. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2618 · Cited by 3,684
Metastasis: from dissemination to organ-specific colonization
Nguyen, D. X., Bos, P. D., & Massagué, J. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2622 · Cited by 2,716
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Aceto, N., Bardia, A., Miyamoto, D. T., Collier, M. D., Wittner, B. S., Spencer, J. A., Yu, M., Pely, A., Engstrom, A., Zhu, H., et al. (2014) · Cell · doi:10.1016/j.cell.2014.07.013 · Cited by 2,516
Metastatic Behavior of Breast Cancer Subtypes
Kennecke, H., Yerushalmi, R., Woods, R., Cheang, M. C. U., Voduc, D., Speers, C. H., Nielsen, T. O., & Gelmon, K. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.25.9820 · Cited by 2,262
Metadata
- 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
- 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
- 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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