title: Epithelial-to-mesenchymal transition confers pericyte properties on cancer cells.
abstract: Carcinoma cells can acquire increased motility and invasiveness through epithelial-to-mesenchymal transition (EMT). However, the significance of EMT in cancer metastasis has been controversial, and the exact fates and functions of EMT cancer cells in vivo remain inadequately understood. Here, we tracked epithelial cancer cells that underwent inducible or spontaneous EMT in various tumor transplantation models. Unlike epithelial cells, the majority of EMT cancer cells were specifically located in the perivascular space and closely associated with blood vessels. EMT markedly activated multiple pericyte markers in carcinoma cells, in particular PDGFR-β and N-cadherin, which enabled EMT cells to be chemoattracted towards and physically interact with endothelium. In tumor xenografts generated from carcinoma cells that were prone to spontaneous EMT, a substantial fraction of the pericytes associated with tumor vasculature were derived from EMT cancer cells. Depletion of such EMT cells in transplanted tumors diminished pericyte coverage, impaired vascular integrity, and attenuated tumor growth. These findings suggest that EMT confers key pericyte attributes on cancer cells. The resulting EMT cells phenotypically and functionally resemble pericytes and are indispensable for vascular stabilization and sustained tumor growth. This study thus proposes a previously unrecognized role for EMT in cancer.
authors.forename: Anitha K
authors.initials: AK
authors.lastname: Shenoy
authors.forename: Yue
authors.initials: Y
authors.lastname: Jin
authors.forename: Huacheng
authors.initials: H
authors.lastname: Luo
authors.forename: Ming
authors.initials: M
authors.lastname: Tang
authors.forename: Christine
authors.initials: C
authors.lastname: Pampo
authors.forename: Rong
authors.initials: R
authors.lastname: Shao
authors.forename: Dietmar W
authors.initials: DW
authors.lastname: Siemann
authors.forename: Lizi
authors.initials: L
authors.lastname: Wu
authors.forename: Coy D
authors.initials: CD
authors.lastname: Heldermon
authors.forename: Brian K
authors.initials: BK
authors.lastname: Law
authors.forename: Lung-Ji
authors.initials: LJ
authors.lastname: Chang
authors.forename: Jianrong
authors.initials: J
authors.lastname: Lu
mesh_terms: D000072283:A549 Cells; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D020286:Pericytes / Q000378:metabolism* / Q000473:pathology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C050361:CDH2 protein, human; D015820:Cadherins; C489083:Cdh2 protein, mouse; D009363:Neoplasm Proteins; C000605860:PDGFRB protein, human; D020797:Receptor, Platelet-Derived Growth Factor beta