Self-Renewal Inhibition in Breast Cancer Stem Cells: Moonlight Role of PEDF in Breast Cancer

Breast cancer is the leading cause of death among females in developed countries. Although the implementation of screening tests and the development of new therapies have increased the probability of remission, relapse rates remain high. Numerous studies have indicated the connection between cancer-...

Full description

Saved in:
Bibliographic Details
Published in:Cancers 2023-11, Vol.15 (22), p.5422
Main Authors: Gil-Gas, Carmen, Sánchez-Díez, Marta, Honrubia-Gómez, Paloma, Sánchez-Sánchez, Jose Luis, Alvarez-Simón, Carmen B, Sabater, Sebastia, Sánchez-Sánchez, Francisco, Ramírez-Castillejo, Carmen
Format: Article
Language:English
Subjects:
Amino acids
Anoikis
Apoptosis
Biomarkers
Breast cancer
Cancer
Cancer therapies
Carcinogenicity
Cell culture
Cell self-renewal
Chemotherapy
Development and progression
Glycoproteins
Metastases
Metastasis
Oncology, Experimental
Patients
Peptides
Phosphorylation
Prevention
Proteins
Quality of life
Remission
Signal transduction
Stem cells
Tumor cells
Tumors
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Breast cancer is the leading cause of death among females in developed countries. Although the implementation of screening tests and the development of new therapies have increased the probability of remission, relapse rates remain high. Numerous studies have indicated the connection between cancer-initiating cells and slow cellular cycle cells, identified by their capacity to retain long labeling (LT+). In this study, we perform new assays showing how stem cell self-renewal modulating proteins, such as PEDF, can modify the properties, percentage of biomarker-expressing cells, and carcinogenicity of cancer stem cells. The PEDF signaling pathway could be a useful tool for controlling cancer stem cells’ self-renewal and therefore control patient relapse, as PEDF enhances resistance in breast cancer patient cells’ in vitro culture. We have designed a peptide consisting of the C-terminal part of this protein, which acts by blocking endogenous PEDF in cell culture assays. We demonstrate that it is possible to interfere with the self-renewal capacity of cancer stem cells, induce anoikis in vivo, and reduce resistance against docetaxel treatment in cancer patient cells in in vitro culture. We have also demonstrated that this modified PEDF protein produces a significant decrease in the percentage of expressed cancer stem cell markers.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers15225422