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Updated: Jul 6, 2025
Author Spotlight: Creating Human Vascularized Micro-Tumors as Models for Translational Cancer Research
Published on: September 15, 2023
Targeting tumor-stromal interactions in triple-negative breast cancer using a human vascularized micro-tumor model
Stephanie J Hachey1, Christopher J Hatch2, Daniela Gaebler3
1Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA. shachey@uci.edu.
Abstract:
Triple-negative breast cancer (TNBC) is highly aggressive with limited available treatments. Stromal cells in the tumor microenvironment (TME) are crucial in TNBC progression; however, understanding the molecular basis of stromal cell activation and tumor-stromal crosstalk in TNBC is limited. To investigate therapeutic targets in the TNBC stromal niche, we used an advanced human in vitro microphysiological system called the vascularized micro-tumor (VMT). Using single-cell RNA sequencing, we revealed that normal breast tissue stromal cells activate neoplastic signaling pathways in the TNBC TME. By comparing interactions in VMTs with clinical data, we identified therapeutic targets at the tumor-stromal interface with potential clinical significance. Combining treatments targeting Tie2 signaling with paclitaxel resulted in vessel normalization and increased efficacy of paclitaxel in the TNBC VMT. Dual inhibition of HER3 and Akt also showed efficacy against TNBC. These data demonstrate the potential of inducing a favorable TME as a targeted therapeutic approach in TNBC.
Insights
Researchers explored triple-negative breast cancer (TNBC) stromal cells using a vascularized micro-tumor model. Targeting tumor-stromal interactions, like Tie2 signaling, shows promise for improving TNBC treatments.
Area of Science:
- Oncology
- Cancer Biology
- Biomedical Engineering
Background:
- Triple-negative breast cancer (TNBC) is aggressive with few treatment options.
- Stromal cells within the tumor microenvironment (TME) significantly influence TNBC progression.
- Limited understanding exists regarding stromal cell activation and tumor-stromal communication in TNBC.
Purpose of the Study:
- To investigate potential therapeutic targets within the TNBC stromal niche.
- To explore tumor-stromal crosstalk using an advanced in vitro model.
Main Methods:
- Utilized a human in vitro microphysiological system: the vascularized micro-tumor (VMT).
- Employed single-cell RNA sequencing to analyze stromal cell activation.
- Integrated VMT data with clinical data to identify therapeutic targets.
Main Results:
- Identified neoplastic signaling pathways activated by normal stromal cells in the TNBC TME.
- Discovered therapeutic targets at the tumor-stromal interface with clinical relevance.
- Demonstrated that combining Tie2 signaling inhibitors with paclitaxel normalized vasculature and enhanced paclitaxel efficacy.
- Showed that dual inhibition of HER3 and Akt was effective against TNBC.
Conclusions:
- The study highlights the potential of targeting the TME as a therapeutic strategy for TNBC.
- Inducing a favorable TME can enhance treatment efficacy for aggressive breast cancers.
- Identified specific molecular targets (Tie2, HER3, Akt) for novel TNBC therapies.
