Abstract
Simple SummaryThe spread of breast cancer to distant parts of the body (metastasis) is the major cause of death in breast cancer patients. Research has shown that apart from the breast cancer cells themselves, other cells and molecules in the vicinity (the tumor microenvironment) also greatly contribute to the ability of breast cancer to metastasize. In this review article, we discuss recent advances in research about how breast cancer cells interact with other cells and molecules around them. We also highlight some new technologies to further unravel the nature of this interaction and how this could be beneficial in developing more effective treatments for advanced breast cancer patients.The tumor microenvironment plays a pivotal role in the tumorigenesis, progression, and metastatic spread of many cancers including breast. There is now increasing evidence to support the observations that a bidirectional interplay between breast cancer cells and stromal cells exists within the tumor and the tumor microenvironment both at the primary tumor site and at the metastatic site. This interaction occurs through direct cell to cell contact, or by the release of autocrine or paracrine factors which can activate pro-tumor signaling pathways and modulate tumor behavior. In this review, we will highlight recent advances in our current knowledge about the multiple interactions between breast cancer cells and neighboring cells (fibroblasts, endothelial cells, adipocytes, innate and adaptive immune cells) in the tumor microenvironment that coordinate to regulate metastasis. We also highlight the role of exosomes and circulating tumor cells in facilitating breast cancer metastasis. We discuss some key markers associated with stromal cells in the breast tumor environment and their potential to predict patient survival and guide treatment. Finally, we will provide some brief perspectives on how current technologies may lead to the development of more effective therapies for the clinical management of breast cancer patients.
Highlights
Adipocytes have been shown to promote mitochondrial metabolism in Breast CancerCurrent ChallengesBreast cancer (BC) cells by downregulating caveolin 1, which increases the secretion of pyruvate and lactate by adipocytes that are taken up by BC cells and cancer-associated fibroblast (CAF) to use as an energy source [52,53]
There is evidence to suggest that gamma-aminobutyric acid (GABA) secreted by neurons can generate reduced nicotiand tumor cell-induced C-C motif ligand 2 (CCL2) expression are associated with the recruitment of pro-metastatic myeloid cells [147,148]
Since accumulating evidence has shown that stromal cells are key players in modulating BC cell behavior at both the primary tumor and metastatic sites, it is not surprising that these same cells greatly influence the course of BC progression
Summary
Breast cancer (BC) affects more than 2.1 million women worldwide each year and accounts for approximately 15% of all cancer-related deaths [1]. It is estimated that 6 to 10% of women diagnosed with BC have stage 4 metastatic BC, and ~85% of them will not survive [2]. Despite significant advances in the treatment of BC, metastatic relapse remains a major challenge for patients, clinicians and breast cancer researchers. These challenges have been further exacerbated by the coronavirus (COVID-19) pandemic. Consultations and treatment of BC patients are delayed [3], providing an ideal situation for tumor progression and metastasis, thereby negatively impacting BC patients’ overall survival. An in-depth understanding of the factors that drive BC metastasis is critical in developing novel therapeutic strategies against the disease
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