Related Experiment Video
Updated: Dec 31, 2025
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Multimodality imaging of TGFbeta signaling in breast cancer metastases
Inna Serganova1, Ekaterina Moroz, Jelena Vider
1Department of Neurology, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10021, USA.
Abstract:
The skeleton is a preferred site for breast cancer metastasis. We have developed a multimodality imaging approach to monitor the transforming growth factor beta (TGFbeta) signaling pathway in bone metastases, sequentially over time in the same animal. As model systems, two MDA-MB-231 breast cancer cells lines with different metastatic tropisms, SCP2 and SCP3, were transduced with constitutive and TGFbeta-inducible reporter genes and were tested in vitro and in living animals. The sites and expansion of metastases were visualized by bioluminescence imaging using a constitutive firefly luciferase reporter, while TGFbeta signaling in metastases was monitored by microPET imaging of HSV1-TK/GFP expression with [(18)F]FEAU and by a more sensitive and cost-effective bioluminescence reporter, based on nonsecreted Gaussia luciferase. Concurrent and sequential imaging of metastases in the same animals provided insight into the location and progression of metastases, and the timing and course of TGFbeta signaling. The anticipated and newly observed differences in the imaging of tumors from two related cell lines have demonstrated that TGFbeta signal transduction pathway activity can be noninvasively imaged with high sensitivity and reproducibility, thereby providing the opportunity for an assessment of novel treatments that target TGFbeta signaling.
Insights
This study developed a novel multimodality imaging technique to track transforming growth factor beta (TGFbeta) signaling in bone metastases from breast cancer. The method allows for sequential monitoring of TGFbeta pathway activity in the same animal over time.
Area of Science:
- Oncology
- Molecular Imaging
- Biotechnology
Background:
- The skeleton is a common site for breast cancer metastasis.
- Monitoring signaling pathways in bone metastases is crucial for understanding disease progression and developing treatments.
- Transforming growth factor beta (TGFbeta) signaling plays a significant role in bone metastasis.
Purpose of the Study:
- To develop and validate a multimodality imaging approach for noninvasively monitoring TGFbeta signaling in bone metastases over time.
- To compare the metastatic tropism and TGFbeta signaling of two related breast cancer cell lines (SCP2 and SCP3).
- To assess the sensitivity and reproducibility of the imaging technique for evaluating TGFbeta pathway activity.
Main Methods:
- Utilized two MDA-MB-231 breast cancer cell lines (SCP2, SCP3) with distinct metastatic tropisms, engineered with constitutive and TGFbeta-inducible reporter genes.
- Employed bioluminescence imaging (BLI) with a firefly luciferase reporter for visualizing metastasis sites and expansion.
- Used microPET imaging with [(18)F]FEAU and a Gaussia luciferase-based BLI reporter to monitor TGFbeta signaling activity.
Main Results:
- Successfully visualized and monitored the location, expansion, and TGFbeta signaling dynamics of bone metastases sequentially in the same animals.
- Demonstrated differences in imaging characteristics between the two cell lines, correlating with their metastatic tropisms and TGFbeta signaling.
- Confirmed high sensitivity and reproducibility in noninvasively imaging TGFbeta signal transduction pathway activity.
Conclusions:
- The developed multimodality imaging approach enables sensitive and reproducible noninvasive monitoring of TGFbeta signaling in bone metastases.
- This technique provides valuable insights into the temporal dynamics of TGFbeta signaling in vivo.
- Offers a powerful tool for assessing the efficacy of novel therapeutic strategies targeting the TGFbeta pathway in breast cancer bone metastasis.
