Cancer Exosomes Trigger Fibroblast to Myofibroblast Differentiation

Webber, Jason P.; Steadman, Robert; Mason, Malcolm David; Tabi, Zsuzsanna; Clayton, Aled

doi:10.1158/0008-5472.can-10-1722

Cited by 697 publications

(548 citation statements)

References 37 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%

“…The generation of CAFs by tumor cellderived exosomes has been described in numerous examples. 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).…”

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

160

124

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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

160

124

View full text Add to dashboard Cite

show abstract

“…Exosomes can be released by different types of cell including cancer cells, fibroblast cells, immune cells and mesenchymal cells. [3][4][5] When shuttled from a donor cell, they can transfer a broad array of biological contents including functional mRNAs, miRNAs, DNA fragments, lipids and proteins to recipient cells. Wrapped in bilayered membranes of exosomes, these contents are much stable even after being transferred to a distant site.…”

Section: Introductionmentioning

confidence: 99%

The exosomes in tumor immunity

2015

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Exosomes are a kind of nanometric membrane vesicles and can be released by almost all kinds of cells, including cancer cells. As the important mediators in intercellular communications, exosomes mediate exchange of protein and genetic material derived from parental cells. Emerging evidences show that exosomes secreted by either host cells or cancer cells are involved in tumor initiation, growth, invasion and metastasis. Moreover, communications between immune cells and cancer cells via exosomes play dual roles in modulating tumor immunity. In this review, we focus on exosome-mediated immunosuppression via inhibition of antitumor responses elicited by immune cells (DCs, NK cells, CD4 C and CD8 C T cells, etc.) and induction of immunosuppressive or regulatory cell populations (MDSCs, Tregs and Bregs). Transfer of cytokines, microRNAs (miRNAs) and functional mRNAs by tumor-derived exosomes (TEXs) is crucial in the immune escape. Furthermore, exosomes secreted from several kinds of immune cells (DCs, CD4 C and CD8 C Tregs) also participate in immunosuppression. On the other hand, we summarize the current application of DCderived and modified tumor-derived exosomes as tumor vaccines. The potential challenges about exosome-based vaccines for clinical application are also discussed.

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“…differentiation into myofibroblasts (28). They foster the interplay of stroma cells with breast tumor cells (29).…”

mentioning

confidence: 99%

Body Fluid Exosomes Promote Secretion of Inflammatory Cytokines in Monocytic Cells via Toll-like Receptor Signaling

Bretz

Ridinger

Rupp

et al. 2013

Journal of Biological Chemistry

207

176

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Background: Exosomes, secreted from cells, have immunomodulatory capacities. Results: NFB-and STAT3-mediated cytokine release is triggered by various types of ex vivo exosomes in a TLR-dependent fashion. Conclusion: Exosomes have inherent signaling capacities important for global inflammatory responses.Significance: Detailed knowledge about intercellular communication in cancer and inflammatory diseases is crucial for development of new therapeutic approaches.

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Cancer Exosomes Trigger Fibroblast to Myofibroblast Differentiation

Cited by 697 publications

References 37 publications

The Multiple Roles of Exosomes in Metastasis

The Multiple Roles of Exosomes in Metastasis

The exosomes in tumor immunity

Body Fluid Exosomes Promote Secretion of Inflammatory Cytokines in Monocytic Cells via Toll-like Receptor Signaling

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