Fra-2 Overexpression Upregulates Pro-metastatic Cell-adhesion Molecules, Promotes Pulmonary Metastasis, and Reduces Survival in a Spontaneous Xenograft Model of Human Breast Cancer

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2021 Oct 25

PMID 34693476

Citations 3

Authors

Sabrina Arnold

Jan Kortland

Diana V Maltseva

Stepan A Nersisyan

Timur R Samatov

Susanne Lezius

Alexander G Tonevitsky

Karin Milde-Langosch

Daniel Wicklein

Udo Schumacher

Christine Sturken

Affiliations

Soon will be listed here.

Abstract

Purpose: The transcription factor Fra-2 affects the invasive potential of breast cancer cells by dysregulating adhesion molecules in vitro. Previous results suggested that it upregulates the expression of E- and P-selectin ligands. Such selectin ligands are important members of the leukocyte adhesion cascade, which govern the adhesion and transmigration of cancer cells into the stroma of the host organ of metastasis. As so far, no in vivo data are available, this study was designed to elucidate the role of Fra-2 expression in a spontaneous breast cancer metastasis xenograft model.

Methods: The effect of Fra-2 overexpression in two stable Fra-2 overexpressing clones of the human breast cancer cell line MDA MB231 on survival and metastatic load was studied after subcutaneous injection into scid and E- and P-selectin-deficient scid mice.

Results: Fra-2 overexpression leads to a significantly shorter overall survival and a higher amount of spontaneous lung metastases not only in scid mice, but also in E- and P-deficient mice, indicating that it regulates not only selectin ligands, but also selectin-independent adhesion processes.

Conclusion: Thus, Fra-2 expression influences the metastatic potential of breast cancer cells by changing the expression of adhesion molecules, resulting in increased adherence to endothelial cells in a breast cancer xenograft model.

Citing Articles

Progress in the Study of Fra-2 in Respiratory Diseases.

Zheng S, Liu Y Int J Mol Sci. 2024; 25(13).

PMID: 39000247 PMC: 11240912. DOI: 10.3390/ijms25137143.

Role of Fra-2 in cancer.

Rampioni Vinciguerra G, Capece M, Scafetta G, Rentsch S, Vecchione A, Lovat F Cell Death Differ. 2023; 31(2):136-149.

PMID: 38104183 PMC: 10850073. DOI: 10.1038/s41418-023-01248-4.

Spontaneous metastasis xenograft models link CD44 isoform 4 to angiogenesis, hypoxia, EMT and mitochondria-related pathways in colorectal cancer.

Everest-Dass A, Nersisyan S, Maar H, Novosad V, Schroder-Schwarz J, Freytag V Mol Oncol. 2023; 18(1):62-90.

PMID: 37849446 PMC: 10766209. DOI: 10.1002/1878-0261.13535.

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