title: Microenvironmental regulation of epithelial-mesenchymal transitions in cancer.
abstract: The evolution of the cancer cell into a metastatic entity is the major cause of death in patients with cancer. Activation of the epithelial-to-mesenchymal transition (EMT) endows invasive and metastatic properties upon cancer cells that favor successful colonization of distal target organs. The observation that in many cancers distant metastases resemble the epithelial phenotype of primary tumors has led to speculation that the disseminated tumor cells recruited to the target organs undergo mesenchymal-to-epithelial transition (MET). However, the MET cascade has not been recapitulated in vivo, and the cellular and molecular regulators that promote MET remain unknown. In a recent report, using a model of spontaneous breast cancer, we have shown that bone marrow-derived myeloid progenitor cells in the premetastatic lung secrete the proteoglycan versican, which induces MET of metastatic tumor cells and accelerates metastases. This review summarizes recent progress in MET research, outlines a unique paracrine cross-talk between the microenvironment and the cancer cells, which promotes tumor outgrowth in the metastatic organ, and discusses opportunities for novel antimetastatic approaches for cancer therapy.
authors.affiliation: Department of Cardiothoracic Surgery, Neuberger Berman Lung Cancer Research Center, Weill Cornell Medical College of Cornell University, New York, New York10065, USA.
authors.forename: Dingcheng
authors.initials: D
authors.lastname: Gao
authors.forename: Linda T
authors.initials: LT
authors.lastname: Vahdat
authors.forename: Stephen
authors.initials: S
authors.lastname: Wong
authors.forename: Jenny C
authors.initials: JC
authors.lastname: Chang
authors.forename: Vivek
authors.initials: V
authors.lastname: Mittal
mesh_terms: D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D059016:Tumor Microenvironment; D053675:Versicans / Q000378:metabolism
chemical_list: D015820:Cadherins; D053675:Versicans