The Cellular and Biological Impact of Extracellular Vesicles in Pancreatic Cancer

Abstract

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.

ANXA1 Contained in EVs Regulates Macrophage Polarization in Tumor Microenvironment and Promotes Pancreatic Cancer Progression and Metastasis

“…THP-1 monocytes were harvested at a number of 5 × 10 5 /mL, differentiated in macrophages M0, treated with PC EVs and then analyzed for CD80, CD86, CD206 and CD163 expressions as reported in [32]. The pellets were incubated for 1 h at room temperature (RT) in PBS 1x containing FBS (2% v/v) and antihuman antibody against CD80, CD86, CD206, CD163 (1:100, Santa Cruz Biotechnologies, Dallas, TX, USA) and then for another hour with conjugated secondary antibody (1:100, antimouse).…”

“…These latter (40-100 nm diameter) are small membranous extracellular vesicles (EVs) released from nonmalignant and malignant cells in the extracellular space and body fluids [21,[25][26][27][28][29][30]. EVs play a central role promoting cell-to-cell communication, cell proliferation, migration and invasion and are involved in organizing premetastatic niches as key modulators of the tumor microenvironment [24,[31][32][33][34][35]. Moreover, previous studies have shown that vesicles regulate the interactions between tumor and immune cells, such as TAMs [32,33].…”

“…EVs play a central role promoting cell-to-cell communication, cell proliferation, migration and invasion and are involved in organizing premetastatic niches as key modulators of the tumor microenvironment [24,[31][32][33][34][35]. Moreover, previous studies have shown that vesicles regulate the interactions between tumor and immune cells, such as TAMs [32,33]. There is limited knowledge about the role of ANXA1-EVs in macrophage polarization in TAMs-M2, as in PC.…”

Peripheral Nerve Decellularization for In Vitro Extracellular Matrix Hydrogel Use: A Comparative Study

“…However, 3D-cultured Schwann cells treated with TEVs (1000 TEVs per Schwann cell) show significant changes in their GFAP to S100 versus both monolayer- ( p < 0.005) and untreated 3D-cultured Schwann cells ( p < 0.0001). Elevated GFAP levels in mature Schwann cells in vivo is correlated with activation following pathophysiological events, such as peripheral nerve injury and cancer invasion. ,, While this relationship has been speculated, there exists limited evidence that TEVs modulate the Schwann cell activation necessary for the onset of perineural invasion . Future studies will investigate specific mechanisms of TEV-mediated Schwann cell activation in cancer settings.…”

“…79,80,85 While this relationship has been speculated, there exists limited evidence that TEVs modulate the Schwann cell activation necessary for the onset of perineural invasion. 86 Future studies will investigate specific mechanisms of TEV-mediated Schwann cell activation in cancer settings. Changes to cell behavior in 2D versus 3D is also evident in dorsal root ganglia neurite cultures, signifying an important characteristic this hydrogel achieves to act as a biomimetic testbed.…”