Epithelial-to-mesenchymal transition confers pericyte properties on cancer cells
Anitha K. Shenoy, Yue Jin, Huacheng Luo, Ming Tang, Christine Pampo, Rong Shao, Dietmar W. Siemann, Lizi Wu, Coy D. Heldermon, Brian K. Law, Lung-Ji Chang, Jianrong Lu
Anitha K. Shenoy, Yue Jin, Huacheng Luo, Ming Tang, Christine Pampo, Rong Shao, Dietmar W. Siemann, Lizi Wu, Coy D. Heldermon, Brian K. Law, Lung-Ji Chang, Jianrong Lu
View: Text | PDF
Research Article Oncology Vascular biology

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

Anitha K. Shenoy, Yue Jin, Huacheng Luo, Ming Tang, Christine Pampo, Rong Shao, Dietmar W. Siemann, Lizi Wu, Coy D. Heldermon, Brian K. Law, Lung-Ji Chang, Jianrong Lu

×

Figure 5

PDGFR-β and N-cadherin are required for EMT cancer cells to associate with endothelial cells in vitro and in vivo.

Options: View larger image (or click on image) Download as PowerPoint
PDGFR-β and N-cadherin are required for EMT cancer cells to associate wi...
(A) Control, PDGFR-β–, or N-cadherin–depleted Hs578T cells (red) were cocultured with HMVECs (green) for tube formation in vitro. EC-bound Hs578T cells are denoted by white arrowheads and quantified (right). (B) Control, PDGFR-β–, or N-cadherin-depleted DCIS-Snail-ER cells (green) were mixed with unlabeled DCIS cells (at a 1:4 ratio) for orthotopic implantation in mice. All tumor-bearing mice received tamoxifen treatment. Tumor sections were stained with Griffonia simplicifolia lectin for vasculature (red). DNA was stained blue with Hoechst 33342. DCIS-Snail-ER cells aligned with vasculature are quantified (right). Scale bars: 50 μm. Error bars represent SD (n = 4–6). *P < 0.05. Statistical differences were determined by 2-tailed Student’s t test.