Exosomes from ovarian cancer cells induce adipose tissue-derived mesenchymal stem cells to acquire the physical and functional characteristics of tumor-supporting myofibroblasts

Cho, Jung Ah; Park, Ho; Lim, Eic Ju; Kim, Kye Hyun; Choi, Joong Sub; Lee, Jung Hoon; Shin, Jae Wook; Lee, Kyo Won

doi:10.1016/j.ygyno.2011.08.005

Cited by 200 publications

(163 citation statements)

References 45 publications

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“…Exosomes released under hypoxic conditions can stimulate angiogenesis through interactions with endothelial cells (EC) (29). Exosomal transforming growth factor β (TGFβ) can induce differentiation of fibroblasts into tumor-supporting myofibroblasts (30) and exosomes from ovarian cancer are able to convert adipose-derived mesenchymal stem cells (MSC) into myofibroblast-like cells, supporting tumor growth and angiogenesis (31). Angiogenesis and myofibroblast-related aspects in the context of metastasis will be discussed in more detail in the following chapters.…”

Section: Exosomes -Functions In Cancermentioning

confidence: 99%

“…Exosomes derived from a variety of cancer cells can induce differentiation of stromal fibroblasts to myofibroblasts by exosome-associated TGFβ and subsequent SMAD-dependent signaling (30,106). Further examples are differentiation of adipose-derived MSCs to myofibroblasts by breast-and ovarian cancer derived exosomes (31,107) and the generation of tumor-supporting fibroblasts from umbilical cord derived MSCs by gastric cancer exosomes (108). In addition, the transfer of MMPinducer EMMPRIN by exosomes derived from lung cancer cells to fibroblasts has been shown to stimulate expression of MMPs, leading to tumor-cell ECM-remodeling, invasion and metastasis (109).…”

Section: Exosome Mediated Interplay Between Tumor Cells With Fibroblamentioning

confidence: 99%

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The Multiple Roles of Exosomes in Metastasis

Weidle

Birzele

Kollmorgen

et al. 2017

CGP

168

133

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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 -Functions In Cancermentioning

confidence: 99%

Section: Exosome Mediated Interplay Between Tumor Cells With Fibroblamentioning

confidence: 99%

The Multiple Roles of Exosomes in Metastasis

Weidle

Birzele

Kollmorgen

et al. 2017

CGP

168

133

View full text Add to dashboard Cite

show abstract

“…Combining cancer-associated MSCs with tumor cells in vivo and in vitro has been shown to result in increased expression of the bone morphogenetic protein (BMP) signaling network, which has several pathologic roles in cancer progression (55). To determine the phenotypic changes that are orchestrated during MSC-to-myofibroblast differentiation, Cho and colleagues treated adipose tissuederived MSCs with exosomes isolated from 2 ovarian cancer cell lines, OVCAR-3 and SKOV-3 (56). Exosome-treated MSCs displayed an elevation of a-SMA expression, which, again, is indicative of an activated fibroblast phenotype, and also resulted in increased production of protumoral cytokines, CXCL12, and TGF-b (56).…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

Revisiting the Complexity of the Ovarian Cancer Microenvironment—Clinical Implications for Treatment Strategies

Musrap

Diamandis

2012

Molecular Cancer Research

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Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies in North American women. Given that EOC encompasses a broad class of tumors consisting of a variety of different histologic and molecular subtypes, which generates genetically and etiologically distinct tumors, several challenges arise during treatment of patients with this disease. Overlaying this complexity is the contribution of supporting cells, particularly stromal components such as fibroblasts and immune infiltrates that collectively create a microenvironment that promotes and enhances cancer progression. A notable example is the induction of angiogenesis, which occurs through the secretion of pro-angiogenic factors by both tumor and tumor-associated cells. The recent development of angiogenic inhibitors targeting tumor vasculature, which have been shown to improve patient outcome when combined with standard therapy, has launched a paradigm shift on how cancer patients should be treated. It is evident that future clinical practices will focus on the incorporation of therapies that antagonize the protumoral effects of such microenvironment contributors. Herein, an overview of the varying tumor-host interactions that influence tumor behavior will be discussed, in addition to the recent efforts undertaken to target these interactions and their potential to revolutionize EOC patient care.

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“…92 However, such differentiation was also found to occur in adipose derived mesenchymal stem cells via exosome mediated pathway in breast and ovarian cancer cells. 93,94 Recently, in an in vitro study, it has been demonstrated that 786-0 renal cancer cell derived exosomes increased migration and invasion capacity of these cells by decreasing the adhesion ability and increasing the expression levels of CXCR4 and MMP-9. 95 Moreover, metastasis promoting epithelial-mesenchymal transition (EMT) related factors, such as vimentin, hepatoma-derived growth factor (HDGF) were found in the plasma membrane and annexin 2, CK2α, and moesin in the lumen of exosomes of bladder cancer respectively, suggesting their crucial involvement in metastatic process.…”

Section: Role In Metastasismentioning

confidence: 99%

Exosomes: Emerging Players of Intercellular Communication in Tumor Microenvironment

et al. 2014

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Seminal discoveries have established the role of complex tumor microenvironment (TME) in cancer progression; and later on also uncovered that vesiculation is an integral part of intercellular communication among various cell types in coordinating the tumor assembly in a dynamic manner. Exosomes are small membrane bound endosomal vesicles, which are classically known for their role in discarding cellular wastes; however, recent reports underlined their novel role in malignancy by their release from cells into the TME. Since then, the role of exosomes have been a subject of increasing interest, as exosome mediated intercellular communications offer a novel reciprocal relationship between cancer and stromal cells within the TME and modulate the fate and function of the recipient cells to finally shape the tumor progression. Exosomes are characterised by different features including size, content and mode of delivery; and its cargo delivers interesting bioactive components in the form of proteins, miRNAs or other molecules to the target cell. In the pursuit of further study of exosomes, it was found that with the help of its distinct bioactive components, exosomes specifically regulate tumor growth, angiogenesis, metastasis as well as drug resistance properties. In fact, it acts as a bridge between different signaling networks, present inside the spatially distant cells of the heterogeneous tumor population. In the current endeavour, we have highlighted the role of exosomes in modulating the intercellular crosstalk during tumor growth and progression, and proposed certain novel roles of exosomes to address the few enigmatic questions of cancer cell biology. Keywords:Exosome, Tumor Microenvironment, Angiogenesis, Metastasis, Drug Resistance Abbreviations:Extracellular vesicles (EV); Tumor Microenvironment (TME); Carcinoma-associated fibroblasts (CAFs); Tumor-associated macrophages (TAM); Transforming growth factor-beta (TGF-β); Vascular endothelial growth factor (VEGF); Endothelial cell (EC); Matrix metalloproteinases (MMPs); Heat shock proteins (HSPs); Cancer stem cells (CSCs); Microvesicles (MVs); Epithelial-mesenchymal transition (EMT); Multi drug resistance-1 (MDR-1); Multidrug resistance associated protein (MRP); ATP-binding cassette transporter (ABC transporter) DISCOVERIES 2014, Jul-Sep, 2(3): e26 DOI: 10.15190/d.2014.18 Exosome mediated intercellular crosstalk in TME www.discoveriesjournals.org 2 ♦ Exosomes comprise of bioactive components such as proteins, RNAs, miRNAs or lipids, and play a pivotal role in modulating tumor niche by controlling intercellular crosstalk.♦ Exosomes mediated intercellular communications and signals within TME regulate tumor growth, angiogenesis, metastasis and drug resistance.

show abstract

Exosomes from ovarian cancer cells induce adipose tissue-derived mesenchymal stem cells to acquire the physical and functional characteristics of tumor-supporting myofibroblasts

Cited by 200 publications

References 45 publications

The Multiple Roles of Exosomes in Metastasis

The Multiple Roles of Exosomes in Metastasis

Revisiting the Complexity of the Ovarian Cancer Microenvironment—Clinical Implications for Treatment Strategies

Exosomes: Emerging Players of Intercellular Communication in Tumor Microenvironment

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