Eta polycaprolactone (ε-PCL) implants appear to cause a partial differentiation of breast cancer lung metastasis in a murine model

Sep 24, 2026

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The study investigates how artificial stroma created by eta polycaprolactone (ε-PCL) implants influences differentiation of breast cancer metastasis cells in a murine model. Cells are conceptualized into stem cell (SC), transient amplifying (TA), and terminally differentiated (TD) compartments, with maturation linked to epithelial stromal interactions. BALB/c mice bearing GFP-labeled 4T1 tumors received ε-PCL implants, with or without VEGF enrichment, followed by flow-cytometry assessment using Ki67 and activated caspase-3 markers.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

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Abstract

Background

Methods

Results

Conclusion

Introduction

Benzon etal. BMC Cancer (2023) 23:343 [https://doi.org/10.1186/s12885-023-10813-6](https://doi.org/10.1186/s12885-023-10813-6) BMC Cancer RESEARCH Open Access Eta polycaprolactone (ε-PCL) implants appear to cause a partial differentiation of breast cancer lung metastasis in a murine model Benjamin Benzon1*, Sandra Marijan2, Matij Pervan3 and Vedrana Čikeš Čulić2 Abstract Background Cells in every epithelium can be roughly divided in three compartments: stem cell (SC) compartment, transient amplifying cell (TA) compartment and terminally differentiated (TD) compartment. Maturation of stem cells is characterized by epithelial stromal interaction and sequential maturational movement of stem cell’s progeny through those compartments. In this work we hypothesize that providing an artificial stroma, which murine breast cancer metastatic cells can infiltrate, will induce their differentiation. Methods BALB/c female mice were injected with 106 isogenic 4T1 breast cancer cells labeled with GFP. After 20 days primary tumors were removed, and artificial ε-PCL implants were implanted on the contralateral side. After 10 more days mice were sacrificed and implants along with lung tissue were harvested. Mice were divided in four groups: tumor removal with sham implantation surgery (n= 5), tumor removal with ε-PCL implant (n= 5), tumor removal with VEGF enriched ε-PCL implant (n= 7) and mice without tumor with VEGF enriched ε-PCL implant (n= 3) . Differentiational status of GFP +cells was assessed by Ki67 and activated caspase 3 expression, thus dividing the population in SC like cells (Ki67+/dim aCasp3 − ), TA like cells (Ki67+/dim aCasp3+/dim ) and TD like cells (Ki67 − aCasp3+/dim ) on flow cytometry. Results Lung metastatic load was reduced by 33% in mice with simple ε-PCL implant when compared to tumor bearing group with no implant. Mice with VEGF enriched implants had 108% increase in lung metastatic load in comparison to tumor bearing mice with no implants. Likewise, amount of GFP +cells was higher in simple ε-PCL implant in comparison to VEGF enriched implants. Differentiation-wise, process of metastasizing to lungs reduces the average fraction of SC like cells when compared to primary tumor. This effect is made more uniform by both kinds of ε-PCL implants. The opposite process is mirrored inTA like cells compartment when it comes to averages. Effects of both types of implants on TD like cells were negligible. Furthermore, if gene expression signatures that mimic tissue compartments are analyzed in human breast cancer metastases, it turns out thatTA signature is associated with increased survival probability. Conclusion ε-PCL implants without VEGF can reduce metastatic loads in lungs, after primary tumor removal. Both types of implants cause lung metastasis differentiation by shifting cancer cells from SC to TA compartment, leaving the TD compartment unaffected. *Correspondence: Benjamin Benzon [bbenzon@mefst.hr](bbenzon@mefst.hr) Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Cr

FAQs

What is the main hypothesis of the study?

Artificial stroma provided by ε-PCL implants that metastatic breast cancer cells infiltrate will induce differentiation of those cells.

How were mice and implants prepared in the experiment?

BALB/c female mice were injected with GFP-labeled isogenic 4T1 breast cancer cells; after 20 days primary tumors were removed and contralateral artificial ε-PCL implants were placed, with groups including VEGF-enriched implants.

What did the results show about lung metastasis and differentiation?

Simple ε-PCL implants reduced lung metastatic load after primary tumor removal, and both implant types shifted cancer cells from SC-like toward TA-like compartments while leaving TD-like cells largely unaffected.

Sep 24, 2026

Uploaded by Aria