The presence of cancer-associated fibroblast in breast cavity side margins is in correlation with the expression of oncoproteins by adjacent epithelial cells - a new era in cancerous potential

Sep 21, 2026

Upload by Miles

Cancer-associated fibroblasts (CAFs) are pivotal tumor-environment cells driving progression and metastasis, including within histologically normal margin areas shaped by field cancerization. The study analyzes breast cavity side margins where oxidative stress pathways (H2O2/ROS) activate MCT1 and MCT4 and link CAF presence to onco-protein activation in adjacent epithelial cells. Non-tumoral margins are tested using carbon-nanotube electrochemical biosensors and followed by RT-PCR, fluorescent, histopathological, and invasion assays.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Abstract

Purpose

Methods

Results

Conclusion

Introduction

Journal of Cancer Research and Clinical Oncology (2024) 150:421 [https://doi.org/10.1007/s00432-024-05943-8](https://doi.org/10.1007/s00432-024-05943-8) The presence of cancer‑associated fibroblast in breast cavity side margins is in correlation with the expression of oncoproteins by adjacent epithelial cells: a new era in cancerous potential Zohreh Sadat Miripour1,2 · Mina Aminifar1 · Parisa Hoseinpour1,3 · Fereshteh Abbasvandi4,5 · Koosha Karimi1 · Alireza Ghahremani1 · Mohammad Parniani4 · Mohammadreza Ghaderinia1 · Faride Makiyan1 · Parisa Aghaee1 · Mohammad Esmaeil Akbari5 · Mohammad Abdolahad1,2,6 Received: 29 June 2024 / Accepted: 4 September 2024 / Published online: 17 September 2024 © The Author(s) 2024 Abstract Purpose Cancer-associated fibroblasts (CAFs) are one of the most critical cells in the tumor environment, with crucial roles in cancer progression and metastasis. Due to Field-Effect phenomena (also called field cancerization), the adjacent cavity side area of the margin is histologically normal, but it has been entered into neoplastic transformation due to MCT4 and MCT1 pathways activated by H2O2/ROS oxidative stress agents secreted by CAF in adjacent tumor bed microenvironment. This paper specifically focused on the role of cancer-associated fibroblast in breast tumor beds and its correlation with the presence of scattered cancer cells or onco-protein-activated cells (may be high risk but not completely transformed cancer cells) in the cavity side margins. Methods In this study, the glycolytic behavior of non-tumoral cavity side margins was examined using carbon nanotubebased electrochemical biosensors integrated into a cancer diagnostic probe. This method enabled the detection of CAF accumulation sites in non-cancerous neighboring tissues of tumors, with a correlation to CAF concentration. Subsequently, RT-PCR, fluorescent, histopathological, and invasion assays were conducted on hyperglycolytic lesions to explore any correlation between the abundance of CAFs and the electrochemical responses of the non-cancerous tissues surrounding the tumor, as well as their neoplastic potential. Results We observed overexpression of cancer-associated transcriptomes as well as the presence and hyperactivation of CAFs in cavity-side regions in which glycolytic metabolism was recorded, independent of the histopathological state of the lesion. At mean 70 .4%, 66.7%, 70 .4%, and 44 .5% increments were observed in GLUT-1, MMP-2, N-cadherin, and MMP-9 transcriptomes by highly glycolytic but histologically cancer-free expression samples in comparison with negative controls (histologically non-cancer lesions with low glycolytic behavior) . Conclusion The presence of CAFs is correlated with the presence of high glycolytic metabolism in the cavity margin lesion, high ROS level in the lesion, and finally aggressive cancer-associated proteins (such as MMP2,…) in the margin while these metabolomes, molecules, and proteins are absent in the margins with negatively scored CDP response and low ROS level. So, it seems that when we observe CAFs in glycolytic lesions with high ROS levels, some high-risk epithelial breast cells may exist while no histological trace of cancer cells was observed. Further research on CAFs could provide valuable insights into the local recurrence of malignant breast diseases. Hence, real-time sensors can be used to detect and investigate CAFsin the non-tumoral regions surrounding tumors in cancer patients, potentially aiding in the prevention of cancer recurrence. Keywords Cancer-associated fibroblast · Field concretization · Cavity side margin · Glycolytic behavior | Zohreh Sadat Miripour and Mohammad Abdolahad contributed equally. | | --- | | Koosha Karimi and Alireza Ghahremani contributed equally. | Extended author information available on the last page of the article Introduction Field cancerization is one of the hot subjects recently presented in cancer biology in which CAFs pla

FAQs

What is the central purpose of the study?

To assess how cancer-associated fibroblasts in breast cavity side margins correlate with oncoprotein expression by adjacent epithelial cells and related high-risk cellular states.

How were non-tumoral cavity side margins evaluated?

Using carbon nanotube-based electrochemical biosensors integrated into a cancer diagnostic probe, followed by RT-PCR, fluorescent, histopathological, and invasion assays.

What key findings connect CAFs with margin risk?

CAF presence aligns with high glycolytic metabolism, elevated ROS, and aggressive cancer-associated proteins (e.g., MMP2, MMP-9) in cavity margins, even when histology shows no cancer traces.

Sep 21, 2026

Upload by Miles