DF/HCC Program Affiliation

Breast Cancer
Angiogenesis, Invasion, and Metastasis

Research Abstract

Our laboratory at the Center for Life Sciences is interested in understanding the crosstalk that operates between the epithelial and the stromal compartments within breast tumors, with particular emphasis on how these interactions influence cancer metastasis. Our recent work indicated that bone-marrow-derived mesenchymal stem cells (MSCs) can home specifically to developing neoplasms where they integrate into the tumor stroma. Within this microenvironment, the tumor-associated MSCs initiate de novo secretion of chemokines which act on the cancer cells and promote their motility, invasion, and metastasis. Current efforts of our group aim to (1) decipher the nature of the cancer-derived systemic signals that affect the bone marrow and how such interactions mobilize MSCs and cause their recruitment to the tumor microenvironment; (2) characterize the nature of the heterotypic interactions that cause the activation of MSCs within the tumor stroma, and (3) elucidate the various mechanisms by which MSCs exert their pro-malignant functions.

Publications

• Karnoub AE,Weinberg RA.Ras oncogenes: split personalities.Nat Rev Mol Cell Biol 2008 Jul;9(7):517-31.
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• Scheel C,Onder T,Karnoub A,Weinberg RA.Adaptation versus selection: the origins of metastatic behavior.Cancer Res 2007 Dec 15;67(24):11476-9; discussion 11479-80.
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• Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA.Mesenchymal stem cells within tumour stroma promote breast cancer metastasis.Nature 2007 Oct 4;449(7162):557-63.
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• Ince TA, Richardson AL, Bell GW, Saitoh M, Godar S, Karnoub AE, Iglehart JD, Weinberg RA.Transformation of different human breast epithelial cell types leads to distinct tumor phenotypes.Cancer Cell 2007 Aug;12(2):160-70.
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• Karnoub AE,Weinberg RA.Chemokine networks and breast cancer metastasis.Breast Dis 2006-2007;26:75-85.
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