Work

Single‐cell transcriptome sequencing reveals SPP1 ‐ CD44 ‐mediated macrophage–tumor cell interactions drive chemoresistance in TNBC

Year: 2024

Type: article

Abstract: Triple‐negative breast cancer (TNBC) is often considered one of the most aggressive subtypes of breast cancer, characterized by a high recurrence rate and low overall survival (OS). It is notorious for posing challenges related to drug resistance. While there has been progress in TNBC research, the mechanisms underlying chemotherapy resistance in TNBC remain largely elusive. We collect single‐cell RNA sequencing (scRNA‐seq) data from five TNBC patients susceptible to chemotherapy and five resistant cases. Comprehensive analyses involving copy number variation (CNV), pseudotime trajectory, cell–cell interactions, pseudospace analysis, as well as transcription factor and functional enrichment are conducted specifically on macrophages and malignant cells. Furthermore, we performed validation experiments on clinical samples using multiplex immunofluorescence. We identified a subset of SPP1 + macrophages that secrete SPP1 signals interacting with CD44 on malignant cell surfaces, potentially activating the PDE3B pathway within malignant cells via the integrin pathway, leading to chemotherapy resistance. The abnormally enhanced SPP1 signal between macrophages and malignant cells may serve as a factor promoting chemotherapy resistance in TNBC patients. Therefore, SPP1 + macrophages could potentially serve as a therapeutic target to reduce chemotherapy resistance.

Source: Journal of Cellular and Molecular Medicine

DOI: 10.1111/jcmm.18525

Authors: Fuzhong Liu, Junfeng Zhang, Xiaowei Gu, Qiuyang Guo, Wenjia Guo

Institutions: Xinjiang Medical University, Tumor Hospital of Xinjiang Medical University, Anhui Medical University

Language: English

Topic: Immune cells in cancer

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,740