Lung metastasis genes couple breast tumor size and metastatic spread.

@article{citeulike:1444220, 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.}, address = {Department of Radiation and Cellular Oncology, Center for Molecular Oncology, and Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL 60637, USA.}, author = {Minn, A. J. and Gupta, G. P. and Padua, D. and Bos, P. and Nguyen, D. X. and Nuyten, D. and Kreike, B. and Zhang, Y. and Wang, Y. and Ishwaran, H. and Foekens, J. A. and van de Vijver, M. and Massagu\'{e}, J. }, citeulike-article-id = {1444220}, doi = {http://dx.doi.org/10.1073/pnas.0701138104}, issn = {0027-8424}, journal = {Proc Natl Acad Sci U S A}, keywords = {breast\_cancer, metastasis}, month = {April}, number = {16}, pages = {6740--6745}, posted-at = {2007-07-09 13:37:38}, priority = {0}, title = {Lung metastasis genes couple breast tumor size and metastatic spread.}, url = {http://dx.doi.org/10.1073/pnas.0701138104}, volume = {104}, year = {2007} }

TY - JOUR ID - citeulike:1444220 L3 - citeulike-article-id:1444220 TI - Lung metastasis genes couple breast tumor size and metastatic spread. JF - Proc Natl Acad Sci U S A VL - 104 IS - 16 SP - 6740 EP - 6745 AD - Department of Radiation and Cellular Oncology, Center for Molecular Oncology, and Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL 60637, USA. SN - 0027-8424 N2 - 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. KW - breast_cancer KW - metastasis AU - Minn, AJ AU - Gupta, GP AU - Padua, D AU - Bos, P AU - Nguyen, DX AU - Nuyten, D AU - Kreike, B AU - Zhang, Y AU - Wang, Y AU - Ishwaran, H AU - Foekens, JA AU - van de Vijver, M AU - Massagué, J PY - 2007/04/17/ UR - http://dx.doi.org/10.1073/pnas.0701138104 ER -