Exosomes Released from Breast Cancer Carcinomas Stimulate Cell Movement

Harris, D. Ahmasi; Patel, Sajni; Guček, Marjan; Hendrix, An; Westbroek, Wendy; Taraska, Justin W.

doi:10.1371/journal.pone.0117495

Cited by 143 publications

(141 citation statements)

References 59 publications

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“…The possible role of breast cancer cell released exosomes in metastasis was supported by the demonstration that exosomes from intermediate-metastatic (MCF-7 transfected with Rab27) and highly metastatic breast cancer cells (MDA-MB-231) could transfer invasion-promoting properties to tumorigenic, but not metastatic MCF-7 breast cancer cells (39). miR-10b was identified as an important component promoting invasion of breast cancer cells (40).…”

Section: Exosomes Derived From Cancer Cells As Mediators Of Migrationmentioning

confidence: 98%

The Multiple Roles of Exosomes in Metastasis

Weidle

Birzele

Kollmorgen

et al. 2017

CGP

160

127

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Abstract. Exosomes are important contributors to cellMetastases are responsible for the death of a large majority of cancer patients despite considerable progress in surgical techniques, radiotherapy, chemotherapy and targeted therapies including immuno-therapy (1). A dramatic reduction of metastatic burden has been observed, however, tumor elimination is almost always incomplete. This phenomenon is based on drug resistance, which is due to adaptation of intracellular pathways or on activation of survival-supporting autocrine and paracrine pathways and several secreted factors expressed by drug-sensitive tumor cells after therapy (2). Metastasis can occur through release of cancer cells from the primary tumor into body cavities that holds true for ovarian and CNS tumors, or via hematogeneous and lymphatic vessels of the circulatory system (3). Metastases of some tumors are directed besides to lymph nodes to mainly one type of organ only, such as prostate cancer to the bones, pancreatic cancer and uveal melanoma to the liver, whereas tumors such as melanoma, breast-and lung cancer can colonize several types of organs (3). Tumor cells have been found in the blood of patients with early-stage cancer and in some cases even before the primary tumor has been diagnosed (4, 5). Recently, making use of single-cell expression profiling, it has been shown that early metastatic cells possess a stem-like gene signature and give rise to heterogeneous metastases (6). The metastatic process is characterized by a defined sequence of events (7,8). Initial steps are detachment from the extracellular matrix (ECM), invasion into the surrounding tissue and proteolysis of the basement membrane. After intravasation, survival of circulating tumor cells (CTCs) is achieved by forming clusters, binding to platelets and immune evasion. Subsequently, they arrest in distal microvascular beds and extravasation can be achieved either by migration through intercellular junctions of endothelial cells (EC) or penetration of a single EC (9). CTCs can also colonize their tumors of origin, a process referred to as "tumor self-seeding", selecting for cancer cell populations more aggressive than those present in the primary tumor (10). After extravasation, colonization and outgrowth in the parenchyma of distant organs are the following steps. A common theme of the metastatic process is settlement of disseminated tumor cells (DTCs) into latency (dormancy), which can last from several months to decades (11). It has been observed that DTCs are recruited into pre-metastatic niches that support their survival by interactions with endothelial, myeloid cells, fibroblasts and other types of cells. After adaptation to the host microenvironment and suppression of an anti-tumoral immune response, DTCs are activated by not yet completely resolved mechanisms. Finally their outgrowth is based on an angiogenic switch mediated by pro-angiogenic factors and establishment of a vascular network to support the metabolic demands of colonizing tumor cells (12). In the follo...

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Section: Exosomes Derived From Cancer Cells As Mediators Of Migrationmentioning

confidence: 98%

The Multiple Roles of Exosomes in Metastasis

Weidle

Birzele

Kollmorgen

et al. 2017

CGP

160

127

View full text Add to dashboard Cite

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“…Alarmingly these tumor-secreted EVs have been demonstrated to transfer partial phenotypic identity to other cancer cells, altering the recipient cell’s migration, invasion, stress-sensitivity (McCready, Sims et al 2010; O’Brien, Rani et al 2013; Melo, Sugimoto et al 2014; Singh, Pochampally et al 2014; Harris, Patel et al 2015), and tissue-tropism (Hoshino, Costa-Silva et al 2015) towards that of the secreting cell, granting the tumor entity a greater overall malignancy than the sum of its parts. EVs secreted by a highly invasive variant of the Hs578T triple negative breast cancer cells increase the proliferation, migration, invasion, and sensitivity to anoikis of other cancer cells in comparison to EVs isolated from the less invasive parental Hs578T (O’Brien, Rani et al 2013), however the mechanism behind these alterations is still unknown.…”

Section: Delivery To Thy Neighbor: Communication Within the Primary Tmentioning

confidence: 99%

Cancer-derived extracellular vesicles: the ‘soil conditioner’ in breast cancer metastasis?

Chin

Wang

2016

Cancer Metastasis Rev

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It has been recognized that cancer-associated mortality is more of a result of the disrupted physiological functions in multiple organs following metastatic dissemination of cancer cells, rather than the presence and growth of the primary tumor. Despite advances in our understanding of the events leading to cancer initiation, growth, and acquisition of invasive properties, we are still unable to effectively treat metastatic disease. It is now being accepted that the secretion of extracellular vesicles, such as exosomes from cancer cells, has a profound impact on the initiation and propagation of metastatic breast cancer. These cancer-secreted vesicles differ from other means of cellular communication due to their capability of bulk delivery and organotropism. Here we provide an overview of the role of extracellular vesicles in breast cancer metastasis and discuss key areas that may facilitate our understanding of metastatic breast cancer to guide our efforts towards providing better therapies.

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“…Exosomes are small membrane vesicles of endocytic origin that are released from various types of cells into the extracellular environment after fusion of multivesicular bodies with the plasma membrane [5]. Recent evidence highlights the ability of tumor-released exosomes to stimulate invasion and migration in various cancer models [4][5][6][7]. Nevertheless, the majority of these studies have been focused on the activity of tumor-related exosomes toward stromal cells or malignant cells from another patient.…”

Section: Introductionmentioning

confidence: 99%