Epithelial-to-mesenchymal transition confers pericyte properties on cancer cells

Area of Science:

• Oncology
• Cell Biology
• Cancer Metastasis Research

Background:

• Epithelial-to-mesenchymal transition (EMT) increases cancer cell motility and invasiveness.
• The in vivo role and fate of EMT cancer cells in metastasis remain unclear.
• EMT's significance in cancer progression is debated.

Purpose of the Study:

• To investigate the in vivo fate and function of cancer cells undergoing EMT.
• To determine if EMT confers pericyte-like characteristics on carcinoma cells.
• To elucidate the role of EMT cancer cells in tumor vascularization and growth.

Main Methods:

• Tracking of epithelial cancer cells undergoing inducible or spontaneous EMT in tumor transplantation models.
• Analysis of EMT cancer cell localization and association with tumor vasculature.
• Assessment of pericyte marker expression (PDGFR-β, N-cadherin) in EMT cells.
• Experimental depletion of EMT cells in transplanted tumors to evaluate effects on vascularization and growth.

Main Results:

• EMT cancer cells preferentially localized to the perivascular space, interacting closely with blood vessels.
• EMT activated pericyte markers in carcinoma cells, facilitating chemoattraction to endothelium.
• EMT cancer cells contributed significantly to tumor pericyte populations in spontaneous EMT models.
• Depletion of EMT cells led to reduced pericyte coverage, impaired vascular integrity, and attenuated tumor growth.

Conclusions:

• EMT confers pericyte-like attributes on cancer cells, enabling vascular interaction and stabilization.
• EMT cancer cells function as pericytes, essential for sustained tumor growth and vascular integrity.
• This study reveals a novel role for EMT in cancer vascularization and progression.