scholarly journals Paracrine interactions between epithelial cells promote colon cancer growth

2020 ◽  
Author(s):  
Guillaume Jacquemin ◽  
Annabelle Wurmser ◽  
Mathilde Huyghe ◽  
Wenjie Sun ◽  
Meghan Perkins ◽  
...  

AbstractTumours are complex ecosystems composed of different types of cells that communicate and influence each other. While the critical role of stromal cells in affecting tumour growth is well established, the impact of mutant cancer cells on healthy surrounding tissues remains poorly defined. Here, we uncovered a paracrine mechanism by which intestinal cancer cells reactivate foetal and regenerative Yap-associated transcriptional programs in neighbouring wildtype epithelial cells, rendering them adapted to thrive in the tumour context. We identified the glycoprotein Thrombospondin-1 (Thbs1) as the essential factor that mediates non-cell autonomous morphological and transcriptional responses. Importantly, Thbs1 is associated with bad prognosis in several human cancers. This study reveals the Thbs1-YAP axis as the mechanistic link mediating paracrine interactions between epithelial cells, promoting tumour formation and progression.

2020 ◽  
Vol 117 (43) ◽  
pp. 26756-26765
Author(s):  
Botai Xuan ◽  
Deepraj Ghosh ◽  
Joy Jiang ◽  
Rachelle Shao ◽  
Michelle R. Dawson

Polyploidal giant cancer cells (PGCCs) are multinucleated chemoresistant cancer cells found in heterogeneous solid tumors. Due in part to their apparent dormancy, the effect of PGCCs on cancer progression has remained largely unstudied. Recent studies have highlighted the critical role of PGCCs as aggressive and chemoresistant cancer cells, as well as their ability to undergo amitotic budding to escape dormancy. Our recent study demonstrated the unique biophysical properties of PGCCs, as well as their unusual migratory persistence. Here we unveil the critical function of vimentin intermediate filaments (VIFs) in maintaining the structural integrity of PGCCs and enhancing their migratory persistence. We performed in-depth single-cell analysis to examine the distribution of VIFs and their role in migratory persistence. We found that PGCCs rely heavily on their uniquely distributed and polarized VIF network to enhance their transition from a jammed to an unjammed state to allow for directional migration. Both the inhibition of VIFs with acrylamide and small interfering RNA knockdown of vimentin significantly decreased PGCC migration and resulted in a loss of PGCC volume. Because PGCCs rely on their VIF network to direct migration and to maintain their enlarged morphology, targeting vimentin or vimentin cross-linking proteins could provide a therapeutic approach to mitigate the impact of these chemoresistant cells in cancer progression and to improve patient outcomes with chemotherapy.


Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2749
Author(s):  
Damian Robert Sojka ◽  
Agnieszka Gogler-Pigłowska ◽  
Katarzyna Klarzyńska ◽  
Marta Klimczak ◽  
Alicja Zylicz ◽  
...  

Heat Shock Protein A2 (HSPA2) is a member of the HSPA (HSP70) chaperone family and has a critical role for male fertility. HSPA2 is present in a number of somatic organs. Limited evidence suggests that HSPA2 may be involved in regulating epithelial cell differentiation. HSPA2 also emerged as a cancer-related chaperone; however, no consensus on its functional significance has been reached so far. In this study, we compared the phenotypic effects of HSPA2 deficit in non-transformed human bronchial epithelial cells (HBEC), and in lung, breast, and cervical cancer cells. We used various techniques to inhibit the HSPA2 gene expression in order to examine the impact of HSPA2 deficiency on cell growth, migration, adhesion, and invasion. Our results show that HBEC but not cancer cells are sensitive to HSPA2 deficit. HSPA2 knockdown in HBEC cells impaired their clone-forming ability and adhesiveness. Thus, our results indicate that epithelial cells can rely on a specific activity of HSPA2, but such dependence can be lost in epithelial cells that have undergone malignant transformation.


Author(s):  
Anne Nassauer

This book provides an account of how and why routine interactions break down and how such situational breakdowns lead to protest violence and other types of surprising social outcomes. It takes a close-up look at the dynamic processes of how situations unfold and compares their role to that of motivations, strategies, and other contextual factors. The book discusses factors that can draw us into violent situations and describes how and why we make uncommon individual and collective decisions. Covering different types of surprise outcomes from protest marches and uprisings turning violent to robbers failing to rob a store at gunpoint, it shows how unfolding situations can override our motivations and strategies and how emotions and culture, as well as rational thinking, still play a part in these events. The first chapters study protest violence in Germany and the United States from 1960 until 2010, taking a detailed look at what happens between the start of a protest and the eruption of violence or its peaceful conclusion. They compare the impact of such dynamics to the role of police strategies and culture, protesters’ claims and violent motivations, the black bloc and agents provocateurs. The analysis shows how violence is triggered, what determines its intensity, and which measures can avoid its outbreak. The book explores whether we find similar situational patterns leading to surprising outcomes in other types of small- and large-scale events: uprisings turning violent, such as Ferguson in 2014 and Baltimore in 2015, and failed armed store robberies.


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2999
Author(s):  
Deborah Reynaud ◽  
Roland Abi Nahed ◽  
Nicolas Lemaitre ◽  
Pierre-Adrien Bolze ◽  
Wael Traboulsi ◽  
...  

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.


Author(s):  
Georgia Colleluori ◽  
Jessica Perugini ◽  
Giorgio Barbatelli ◽  
Saverio Cinti

AbstractThe mammary gland (MG) is an exocrine gland present in female mammals responsible for the production and secretion of milk during the process of lactation. It is mainly composed by epithelial cells and adipocytes. Among the features that make the MG unique there are 1) its highly plastic properties displayed during pregnancy, lactation and involution (all steps belonging to the lactation cycle) and 2) its requirement to grow in close association with adipocytes which are absolutely necessary to ensure MG’s proper development at puberty and remodeling during the lactation cycle. Although MG adipocytes play such a critical role for the gland development, most of the studies have focused on its epithelial component only, leaving the role of the neighboring adipocytes largely unexplored. In this review we aim to describe evidences regarding MG’s adipocytes role and properties in physiologic conditions (gland development and lactation cycle), obesity and breast cancer, emphasizing the existing gaps in the literature which deserve further investigation.


2021 ◽  
pp. 1-21
Author(s):  
Davide Vittori

Abstract Scholars have long debated whether populism harms or improves the quality of democracy. This article contributes to this debate by focusing on the impact of populist parties in government. In particular, it inquires: (1) whether populists in government are more likely than non-populists to negatively affect the quality of democracies; (2) whether the role of populists in government matters; and (3) which type of populism is expected to negatively affect the quality of liberal-democratic regimes. The results find strong evidence that the role of populists in government affects several qualities of democracy. While robust, the findings related to (2) are less clear-cut than those pertaining to (1). Finally, regardless of their role in government, different types of populism have different impacts on the qualities of democracy. The results show that exclusionary populist parties in government tend to have more of a negative impact than other forms of populism.


2021 ◽  
pp. 003329412110021
Author(s):  
Sizhe Liu ◽  
Wei Zhang ◽  
Xianyou He ◽  
Xiaoxiang Tang ◽  
Shuxian Lai ◽  
...  

There is evidence that greater aesthetic experience can be linked to artworks when their corresponding meanings can be successfully inferred and understood. Modern cultural-expo architecture can be considered a form of artistic creation and design, and the corresponding design philosophy may be derived from representational objects or abstract social meanings. The present study investigates whether cultural-expo architecture with an easy-to-understand architectural appearance design is perceived as more beautiful and how architectural photographs and different types of descriptions of architectural appearance designs interact and produce higher aesthetic evaluations. The results showed an obvious aesthetic preference for cultural-expo architecture with an easy-to-understand architectural appearance design (Experiment 1). Moreover, we found that the aesthetic rating score of architectural photographs accompanied by an abstract description was significantly higher than that of those accompanied by a representational description only under the difficult-to-understand design condition (Experiment 2). The results indicated that people preferred cultural-expo architecture with an easy-to-understand architectural appearance design due to a greater understanding of the design, providing further evidence that abstract descriptions can provide supplementary information and explanation to enhance the sense of beauty of abstract cultural-expo architecture.


Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 933
Author(s):  
Andrea Gila-Diaz ◽  
Gloria Herranz Carrillo ◽  
Pratibha Singh ◽  
David Ramiro-Cortijo

Cardiovascular disease remains a leading cause of mortality worldwide. Unresolved inflammation plays a critical role in cardiovascular diseases development. Specialized Pro-Resolving Mediators (SPMs), derived from long chain polyunsaturated fatty acids (LCPUFAs), enhances the host defense, by resolving the inflammation and tissue repair. In addition, SPMs also have anti-inflammatory properties. These physiological effects depend on the availability of LCPUFAs precursors and cellular metabolic balance. Most of the studies have focused on the impact of SPMs in adult cardiovascular health and diseases. In this review, we discuss LCPUFAs metabolism, SPMs, and their potential effect on cardiovascular health and diseases primarily focusing in neonates. A better understanding of the role of these SPMs in cardiovascular health and diseases in neonates could lead to the development of novel therapeutic approaches in cardiovascular dysfunction.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 74-74
Author(s):  
Lun Li ◽  
Yeonjung Lee ◽  
Daniel W L Lai

Abstract Compared to men, women undertake more family caregiving responsibilities, and thus take more toll in health and wellbeing when they are employed. The current study examined the gender difference in mental health among employed family caregivers, focusing on the role of workplace support in balancing work and caregiving roles. Guided by the social role theory and the moderated-mediation model of employment adjustment and mental health, we analyzed a nationally representative data from the 2012 Canada General Social Survey - Caregiving and Care Receiving with a sample of 2,426 participants selected. Moderated-mediation analysis based on the SPSS macro PROCESS 3.3 was used. Women employed family caregivers are more likely to undertake higher intensive caregiving, make more employment adjustment, and further report worse mental health status than their men counterparts. Gender difference was apparent in regards to the workplace support. For women, the moderating effect of workplace support is significant only when there are at least 5 different types of workplace support available at their workplaces, while for men, the moderating effect is significant when there are at least 2-3 different types of workplace support available. Women employed family caregivers experience worse mental health when employment adjustment is needed for their care responsibility. Findings have implications for providing workplace support for family caregivers given that women benefit less from workplace support compared to men. Further study is needed to explore the impact of various types of workplace support for women employed family caregivers, and to provide tailored support to them.


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