Small extracellular vesicles: from mediating cancer cell metastasis to therapeutic value in pancreatic cancer

AbstractPancreatic cancer is a highly malignant tumor and, is extremely difficult to diagnose and treat. Metastasis is one of the critical steps in the development of cancer and uses cell to cell communication to mediate changes in the microenvironment. Small extracellular vesicles (sEVs)-carry proteins, nucleic acids and other bioactive substances, and are important medium for communication between cells. There are two primary steps in sVEs-mediated metastasis: communication between pancreatic cancer cells and their surrounding microenvironment; and the communication between primary tumor cells and distant organ cells in distant organs that promotes angiogenesis, reshaping extracellular matrix, forming immunosuppressive environment and other ways to form appropriate pre-metastasis niche. Here, we explore the mechanism of localization and metastasis of pancreatic cancer and use sEVs as early biomarkers for the detection and treatment of pancreatic cancer. Graphical Abstract

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Comparative Evaluation of Methods for Isolating Small Extracellular Vesicles Derived from Pancreatic Cells

10.21203/rs.3.rs-110539/v1 ◽

2020 ◽

Author(s):

Jie-Min Wang ◽

Yong-Jiang Li ◽

Jun-Yong Wu ◽

Jia-Xin Cai ◽

Jing Wen ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Density Gradient ◽

Extracellular Vesicles ◽

Cell Communication ◽

Size Exclusion ◽

Density Gradient Ultracentrifugation ◽

Pancreatic Cancer Cells ◽

Co Precipitation ◽

Therapeutic Study

Abstract Background: Small extracellular vesicles (sEVs) are nanosized vesicles involved in cell-to-cell communication. sEVs have been widely studied for clinical applications such as early detection of diseases and as therapeutics. Various methods for sEVs isolation have been using, but different methods may result in different qualities of sEVs and impact downstream analysis and applications. Here, we compared current isolation methods and performed a comparative analysis of sEVs derived from pancreatic cancer cells.Results: Ultracentrifugation, ultrafiltration and co-precipitation as concentration methods were firstly evaluated for yield, size, morphology and protein level of pellets. Then, isolate sEVs obtained by four different purification methods: size exclusion chromatography, density gradient ultracentrifugation, ultracentrifugation, and immunoaffinity capturing, were analysed and compared. For the concentration process, ultracentrifugation method obtained high quality and concentration pellets. For the purification process, immunoaffinity capturing method obtained the purest sEVs with less contaminants, while density gradient ultracentrifugation-based method obtained sEVs with the smallest size. Proteomic analysis revealed distinct protein contents of purified sEVs. Conclusions: For isolating sEVs derived from pancreatic cancer cells, ultracentrifugation-based method is recommended for concentration of sEVs, density gradient ultracentrifugation-based method may be suitable for isolation of sEVs for therapeutic study, immunoaffinity capturing may be applied for studies exploring sEVs as biomarkers.

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Cell‑to‑cell communication via extracellular vesicles among human pancreatic cancer cells derived from the same patient

Molecular Medicine Reports ◽

10.3892/mmr.2018.9376 ◽

2018 ◽

Cited By ~ 1

Author(s):

Mitsuru Chiba ◽

Shiori Kubota ◽

Ayaka Sakai ◽

Satoru Monzen

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Extracellular Vesicles ◽

Cell Communication ◽

Human Pancreatic Cancer ◽

Pancreatic Cancer Cells

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Extracellular Vesicles (EVs) and Pancreatic Cancer: From the Role of EVs to the Interference with EV-Mediated Reciprocal Communication

Biomedicines ◽

10.3390/biomedicines8080267 ◽

2020 ◽

Vol 8 (8) ◽

pp. 267 ◽

Cited By ~ 2

Author(s):

Sokviseth Moeng ◽

Seung Wan Son ◽

Jong Sun Lee ◽

Han Yeoung Lee ◽

Tae Hee Kim ◽

...

Keyword(s):

Pancreatic Cancer ◽

Extracellular Vesicles ◽

Immune Cells ◽

Essential Role ◽

Therapeutic Strategy ◽

Cell Communication ◽

Therapeutic Resistance ◽

Extracellular Biosynthesis ◽

Pancreatic Cancer Cells

Pancreatic cancer is malignant and the seventh leading cause of cancer-related deaths worldwide. However, chemotherapy and radiotherapy are—at most—moderately effective, indicating the need for new and different kinds of therapies to manage this disease. It has been proposed that the biologic properties of pancreatic cancer cells are finely tuned by the dynamic microenvironment, which includes extracellular matrix, cancer-associated cells, and diverse immune cells. Accumulating evidence has demonstrated that extracellular vesicles (EVs) play an essential role in communication between heterogeneous subpopulations of cells by transmitting multiplex biomolecules. EV-mediated cell–cell communication ultimately contributes to several aspects of pancreatic cancer, such as growth, angiogenesis, metastasis and therapeutic resistance. In this review, we discuss the role of extracellular vesicles and their cargo molecules in pancreatic cancer. We also present the feasibility of the inhibition of extracellular biosynthesis and their itinerary (release and uptake) for a new attractive therapeutic strategy against pancreatic cancer.

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The Cellular and Biological Impact of Extracellular Vesicles in Pancreatic Cancer

Cancers ◽

10.3390/cancers13123040 ◽

2021 ◽

Vol 13 (12) ◽

pp. 3040

Author(s):

Zainab Hussain ◽

Jeremy Nigri ◽

Richard Tomasini

Keyword(s):

Pancreatic Cancer ◽

Tumor Cells ◽

Extracellular Vesicles ◽

Cell Communication ◽

Pancreatic Tumors ◽

Mediated Communication ◽

Biological Impact ◽

Physiological Relevance ◽

Cellular Components ◽

Tumoral Cells

Deciphering the interactions between tumor and stromal cells is a growing field of research to improve pancreatic cancer-associated therapies and patients’ care. Indeed, while accounting for 50 to 90% of the tumor mass, many pieces of evidence reported that beyond their structural role, the non-tumoral cells composing the intra-tumoral microenvironment influence tumor cells’ proliferation, metabolism, cell death and resistance to therapies, among others. Simultaneously, tumor cells can influence non-tumoral neighboring or distant cells in order to shape a tumor-supportive and immunosuppressive environment as well as influencing the formation of metastatic niches. Among intercellular modes of communication, extracellular vesicles can simultaneously transfer the largest variety of signals and were recently reported as key effectors of cell–cell communication in pancreatic cancer, from its development to its evolution as well as its ability to resist available treatments. This review focuses on extracellular vesicles-mediated communication between different cellular components of pancreatic tumors, from the modulation of cellular activities and abilities to their biological and physiological relevance. Taking into consideration the intra-tumoral microenvironment and its extracellular-mediated crosstalk as main drivers of pancreatic cancer development should open up new therapeutic windows.

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Exosomes: the key of sophisticated cell–cell communication and targeted metastasis in pancreatic cancer

Cell Communication and Signaling ◽

10.1186/s12964-021-00808-w ◽

2022 ◽

Vol 20 (1) ◽

Author(s):

Huan Zhang ◽

Juan Xing ◽

Zhujiang Dai ◽

Daorong Wang ◽

Dong Tang

Keyword(s):

Pancreatic Cancer ◽

Cell Communication ◽

Ecological Niches ◽

Clinical Value ◽

Growth And Survival ◽

Pancreatic Cancer Cells ◽

Intercellular Communications ◽

Multiple Signaling ◽

Treatment And Diagnosis ◽

Methods Of Treatment

AbstractPancreatic cancer is one of the most common malignancies. Unfortunately, the lack of effective methods of treatment and diagnosis has led to poor prognosis coupled with a very high mortality rate. So far, the pathogenesis and progression mechanisms of pancreatic cancer have been poorly characterized. Exosomes are small vesicles secreted by most cells, contain lipids, proteins, and nucleic acids, and are involved in diverse functions such as intercellular communications, biological processes, and cell signaling. In pancreatic cancer, exosomes are enriched with multiple signaling molecules that mediate intercellular communication with control of immune suppression, mutual promotion between pancreas stellate cells and pancreatic cancer cells, and reprogramming of normal cells. In addition, exosomes can regulate the pancreatic cancer microenvironment and promote the growth and survival of pancreatic cancer. Exosomes can also build pre-metastatic micro-ecological niches and facilitate the targeting of pancreatic cancer. The ability of exosomes to load cargo and target allows them to be of great clinical value as a biomarker mediator for targeted drugs in pancreatic cancer.

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Pancreatic Cancer Cells Invasiveness is Mainly Affected by Interleukin-1β not by Transforming Growth Factor-β1

The International Journal of Biological Markers ◽

10.1177/172460080502000406 ◽

2005 ◽

Vol 20 (4) ◽

pp. 235-241 ◽

Cited By ~ 22

Author(s):

E. Greco ◽

D. Basso ◽

P. Fogar ◽

S. Mazza ◽

F. Navaglia ◽

...

Keyword(s):

Pancreatic Cancer ◽

Extracellular Matrix ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Pancreatic Cancer Cell ◽

Matrigel Invasion ◽

Matrix Adhesion ◽

Pancreatic Cancer Cells ◽

Tgf Β1

Background We investigated in vitro whether IL-1β and TGF-β1 affect pancreatic cancer cell growth, adhesion to the extracellular matrix and Matrigel invasion. Materials and methods Adhesion to fibronectin, laminin and type I collagen, and Matrigel invasion after stimulation with saline, IL-1β and TGF-β1 were evaluated using three primary and three metastatic pancreatic cancer cell lines. Results Extracellular matrix adhesion of control cells varied independently of the metastatic characteristics of the studied cell lines, whereas Matrigel invasion of control cells was partly correlated with the in vivo metastatic potential. IL-1β did not influence extracellular matrix adhesion, whereas it significantly enhanced the invasiveness of three of the six cell lines. TGF-β1 affected the adhesion of one cell line, and exerted contrasting effects on Matrigel invasion of different cell lines. Conclusions IL-1β enhances the invasive capacity of pancreatic cancer cells, whereas TGF-β1 has paradoxical effects on pancreatic cancer cells; this makes it difficult to interfere with TGF-β1 signaling in pancreatic cancer treatment.

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Fountain of youth of pancreatic cancer cells: the extracellular matrix

Cell Death Discovery ◽

10.1038/s41420-017-0004-7 ◽

2018 ◽

Vol 4 (1) ◽

Cited By ~ 9

Author(s):

Victoire Gouirand ◽

Sophie Vasseur

Keyword(s):

Pancreatic Cancer ◽

Extracellular Matrix ◽

Cancer Cells ◽

Pancreatic Cancer Cells ◽

Fountain Of Youth

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Comparative Evaluation of Methods for Isolating Small Extracellular Vesicles Derived from Pancreatic Cancer Cells

10.21203/rs.3.rs-110539/v2 ◽

2021 ◽

Author(s):

Jie-Min Wang ◽

Yong-Jiang Li ◽

Jun-Yong Wu ◽

Jia-Xin Cai ◽

Jing Wen ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Density Gradient ◽

Extracellular Vesicles ◽

Pancreatic Cancer Cell Line ◽

Size Exclusion ◽

Density Gradient Ultracentrifugation ◽

High Concentration ◽

Protein Marker ◽

Pancreatic Cancer Cells

Abstract Background: Small extracellular vesicles (sEVs) are nanosized vesicles involved in cell-to-cell communication. sEVs have been widely studied for clinical applications such as early detection of diseases and as therapeutics. Various methods for sEVs isolation are been using, but different methods may result in different qualities of sEVs and impact downstream analysis and applications. Here, we compared current isolation methods and performed a comparative analysis of sEVs from supernatant of cultured pancreatic cancer cells.Methods: Ultracentrifugation, ultrafiltration and co-precipitation as concentration methods were firstly evaluated for yield, size, morphology and protein level of pellets. Then, isolate sEVs obtained by four different purification methods: size exclusion chromatography, density gradient ultracentrifugation, ultracentrifugation, and immunoaffinity capturing, were analysed and compared.Results: For the concentration process, ultracentrifugation method obtained high quality and high concentration of pellets. For the purification process, immunoaffinity capturing method obtained the purest sEVs with less contaminants, while density gradient ultracentrifugation-based method obtained sEVs with the smallest size. Proteomic analysis revealed distinct protein contents of purified sEVs from different methods. Conclusions: For isolating sEVs derived from supernatant of cultured pancreatic cancer cell line, ultracentrifugation-based method is recommended for concentration of sEVs, density gradient ultracentrifugation-based method may be applied for obtaining purified sEVs with controlled size, immunoaffinity capturing may be suitable for studies requiring sEVs with high purity but may loss subtypes of sEVs without specific protein marker.

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