Influence of Extracellular Vesicles on Lung Stromal Cells during Breast Cancer Metastasis

Abstract

Breast cancer is a prominent cause of cancer diagnosis and death in women globally, with over 90% of deaths being attributed to complications that arise from metastasis. One of the common locations for breast cancer metastasis is the lung, which is associated with significant morbidity and mortality. Curative treatments for metastatic breast cancer patients are not available and the molecular mechanisms that underlie lung metastasis are not fully understood. In order to better treat these patients, identifying events that occur both prior to and during metastatic spread to the lung is essential. Several studies have demonstrated that breast cancer-derived extracellular vesicles secreted from the primary breast tumor play a key role in establishing the lung pre-metastatic niche to support colonization of metastatic tumor cells. In this review, we summarize recent work supporting the influence of extracellular vesicles on stromal components of the lung to construct the pre-metastatic niche and support metastasis. Furthermore, we discuss the potential clinical applications of utilizing extracellular vesicles for diagnosis and treatment. Together, this review highlights the dynamic nature of extracellular vesicles, their roles in breast cancer metastasis to the lung, and their value as potential biomarkers and therapeutics for cancer prevention.

Non-invasive detection of orthotopic human lung tumors by microRNA expression profiling of mouse exhaled breath condensates and exhaled extracellular vesicles

“…In order to improve the clinical detection of secondary lung cancers and to complement current imaging strategies, recent research efforts have led to the development of robust non-symptom-driven molecular screening assays. These assays have been designed to detect circulating primary tumor bioproducts such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating RNA transcripts (i.e., circular RNAs, messenger RNAs (mRNA), microRNAs (miRNA) and long non-coding RNAs), and more recently circulating tumor extracellular vesicles (EVs) [12][13][14][15][16][17][18] . Although the detection of CTCs has been used prognostically, it is not foolproof and a significant subset of patients who develop metastatic disease are not identified using this approach [19][20][21][22] .…”

Triple-Negative Breast Cancer EVs Modulate Growth and Migration of Normal Epithelial Lung Cells

“…Thus, EVs may be used as reliable biomarkers for early cancer detection and cancer development [ 15 , 16 ]. There is growing evidence that tumor-derived EVs can promote angiogenesis by regulating the activity of endothelial cells at distant secondary sites to facilitate metastasis [ 17 ]. In this regard, EVs’ cargo may be associated with cancer progression; in fact, recent studies showed that EVs induce epithelial mesenchymal transition (EMT) via the modulation of Hippo tumor suppressor signaling pathway in breast cancer [ 18 ].…”