Differential Gene Expression of Fresh Tissue and Patient-Derived Explants’ Matricellular Proteins Augment Inflammatory Breast Cancer Metastasis: The Possible Role of IL-6 and MCP-1

Authors

Alshaimaa Tarek
Hossam Taha Mohamed
Aya Ali El-Sharkawy
Shrouk Khalaf El-Sayed
Jon Mark Hirshon
Wendy A Woodward
Mohamed El-Shinawi
Mona Mostafa Mohamed

Publication Date

5-27-2023

Journal

QJM: An International Journal of Medicine

Abstract

BACKGROUND: Matricellular proteins comprising matrisome and adhesome are responsible for structure integrity and interactions between cells in the tumour microenvironment of breast cancer. Changes in the gene expression of matrisome and adhesome augment metastasis. Since inflammatory breast cancer (IBC) is characterized by high metastatic behaviour. Herein, we compared the gene expression profile of matrisome and adhesome in non-IBC and IBC in fresh tissue and ex vivo patient-derived explants (PDEs) and we also compared the secretory inflammatory mediators of PDEs in non-IBC and IBC to identify secretory cytokines participate in cross-talk between cells via interactions with matrisome and adhisome.

METHODS: Fifty patients (31 non-IBC and 19 IBC) were enrolled in the present study. To test their validation in clinical studies, PDEs were cultured as an ex vivo model. Gene expression and cytokine array were used to identify candidate genes and cytokines contributing to metastasis in the examined fresh tissues and PDEs. Bioinformatics analysis was applied on identified differentially expressed genes using GeneMANIA and Metascape gene annotation and analysis resource to identify pathways involved in IBC metastasis.

RESULTS: Normal and cancer fresh tissues and PDEs of IBC were characterized by overexpression of CDH1 and MMP14 and downregulation of CTNNA1 and TIMP1 compared with non-IBC. The secretome of IBC cancer PDEs is characterized by significantly high expression of interleukin 6 and monocyte chemoattractant protein-1 (CCL2) compared with non-IBC.

CONCLUSION: Genes expressed by adhisome and matrisome play a significant role in IBC metastasis and should be considered novel target therapy.

Keywords

Humans, Inflammatory Breast Neoplasms, Interleukin-6, Chemokine CCL2, Cytokines, Gene Expression, Tumor Microenvironment

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Associated Data

PMID: 36592055