Investigation of Cancer Cell Extravasation Through mRNA Analysis of Organ-specific Endothelial Cells and Microfluidics

Author(s):  
2011 ◽  
Vol 108 (32) ◽  
pp. 13147-13152 ◽  
Author(s):  
Katrin J. Svensson ◽  
Paulina Kucharzewska ◽  
Helena C. Christianson ◽  
Stefan Sköld ◽  
Tobias Löfstedt ◽  
...  

2017 ◽  
Vol 32 (1) ◽  
pp. 276-288 ◽  
Author(s):  
Wenwen Zhang ◽  
Jing Xu ◽  
Hehui Fang ◽  
Lin Tang ◽  
Weiwei Chen ◽  
...  

2005 ◽  
Vol 174 (9) ◽  
pp. 5573-5582 ◽  
Author(s):  
Aleksandra Bielawska-Pohl ◽  
Claire Crola ◽  
Anne Caignard ◽  
Catherine Gaudin ◽  
Danuta Dus ◽  
...  

2020 ◽  
Vol 21 (20) ◽  
pp. 7619 ◽  
Author(s):  
Jan Korbecki ◽  
Szymon Grochans ◽  
Izabela Gutowska ◽  
Katarzyna Barczak ◽  
Irena Baranowska-Bosiacka

CC chemokines (or β-chemokines) are 28 chemotactic cytokines with an N-terminal CC domain that play an important role in immune system cells, such as CD4+ and CD8+ lymphocytes, dendritic cells, eosinophils, macrophages, monocytes, and NK cells, as well in neoplasia. In this review, we discuss human CC motif chemokine ligands: CCL1, CCL3, CCL4, CCL5, CCL18, CCL19, CCL20, CCL21, CCL25, CCL27, and CCL28 (CC motif chemokine receptor CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 ligands). We present their functioning in human physiology and in neoplasia, including their role in the proliferation, apoptosis resistance, drug resistance, migration, and invasion of cancer cells. We discuss the significance of chemokine receptors in organ-specific metastasis, as well as the influence of each chemokine on the recruitment of various cells to the tumor niche, such as cancer-associated fibroblasts (CAF), Kupffer cells, myeloid-derived suppressor cells (MDSC), osteoclasts, tumor-associated macrophages (TAM), tumor-infiltrating lymphocytes (TIL), and regulatory T cells (Treg). Finally, we show how the effect of the chemokines on vascular endothelial cells and lymphatic endothelial cells leads to angiogenesis and lymphangiogenesis.


2020 ◽  
Vol 22 (4) ◽  
Author(s):  
Andrew Przysinda ◽  
Wei Feng ◽  
Guang Li

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1946 ◽  
Author(s):  
Junyu Cen ◽  
Lingyun Feng ◽  
Huichuan Ke ◽  
Lifeng Bao ◽  
Lin Z. Li ◽  
...  

Transendothelial migration of malignant cells plays an essential role in tumor progression and metastasis. The present study revealed that treating human umbilical vein endothelial cells (HUVECs) with exosomes derived from metastatic breast cancer cells increased the number of cancer cells migrating through the endothelial cell layer and impaired the tube formation of HUVECs. Furthermore, the expression of intercellular junction proteins, including vascular endothelial cadherin (VE-cadherin) and zona occluden-1 (ZO-1), was reduced significantly in HUVECs treated with carcinoma-derived exosomes. Proteomic analyses revealed that thrombospondin-1 (TSP1) was highly expressed in breast cancer cell MDA-MB-231-derived exosomes. Treating HUVECs with TSP1-enriched exosomes similarly promoted the transendothelial migration of malignant cells and decreased the expression of intercellular junction proteins. TSP1-down regulation abolished the effects of exosomes on HUVECs. The migration of breast cancer cells was markedly increased in a zebrafish in vivo model injected with TSP1-overexpressing breast cancer cells. Taken together, these results suggest that carcinoma-derived exosomal TSP1 facilitated the transendothelial migration of breast cancer cells via disrupting the intercellular integrity of endothelial cells.


2020 ◽  
Vol 319 (1) ◽  
pp. F41-F51
Author(s):  
Tianzi Zhang ◽  
Daniel Lih ◽  
Ryan J. Nagao ◽  
Jun Xue ◽  
Erwin Berthier ◽  
...  

Endothelial cells (ECs) from different human organs possess organ-specific characteristics that support specific tissue regeneration and organ development. EC specificity is identified by both intrinsic and extrinsic cues, among which the parenchyma and organ-specific microenvironment are critical contributors. These extrinsic cues are, however, largely lost during ex vivo cultures. Outstanding challenges remain to understand and reestablish EC organ specificity for in vitro studies to recapitulate human organ-specific physiology. Here, we designed an open microfluidic platform to study the role of human kidney tubular epithelial cells in supporting EC specificity. The platform consists of two independent cell culture regions segregated with a half wall; culture media are added to connect the two culture regions at a desired time point, and signaling molecules can travel across the half wall (paracrine signaling). Specifically, we report that in the microscale coculture device, primary human kidney proximal tubule epithelial cells (HPTECs) rescued primary human kidney peritubular microvascular EC (HKMEC) monolayer integrity and fenestra formation and that HPTECs upregulated key HKMEC kidney-specific genes (hepatocyte nuclear factor 1 homeobox B, adherens junctions-associated protein 1, and potassium voltage-gated channel subfamily J member 16) and endothelial activation genes (vascular cell adhesion molecule-1, matrix metalloproteinase-7, and matrix metalloproteinase-10) in coculture. Coculturing with HPTECs also promoted kidney-specific genotype expression in human umbilical vein ECs and human pluripotent stem cell-derived ECs. Compared with culture in HPTEC conditioned media, coculture of ECs with HPTECs showed increased upregulation of kidney-specific genes, suggesting potential bidirectional paracrine signaling. Importantly, our device is compatible with standard pipettes, incubators, and imaging readouts and could also be easily adapted to study cell signaling between other rare or sensitive cells.


2017 ◽  
Vol 215 (1) ◽  
pp. 35-49 ◽  
Author(s):  
Tatiana V. Petrova ◽  
Gou Young Koh

Recent discoveries of novel functions and diverse origins of lymphatic vessels have drastically changed our view of lymphatic vasculature. Traditionally regarded as passive conduits for fluid and immune cells, lymphatic vessels now emerge as active, tissue-specific players in major physiological and pathophysiological processes. Lymphatic vessels show remarkable plasticity and heterogeneity, reflecting their functional specialization to control the tissue microenvironment. Moreover, alternative developmental origins of lymphatic endothelial cells in some organs may contribute to the diversity of their functions in adult tissues. This review aims to summarize the most recent findings of organotypic differentiation of lymphatic endothelial cells in terms of their distinct (patho)physiological functions in skin, lymph nodes, small intestine, brain, and eye. We discuss recent advances in our understanding of the heterogeneity of lymphatic vessels with respect to the organ-specific functional and molecular specialization of lymphatic endothelium, such as the hybrid blood-lymphatic identity of Schlemm’s canal, functions of intestinal lymphatics in dietary fat uptake, and discovery of meningeal lymphatic vasculature and perivascular brain lymphatic endothelial cells.


Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2850
Author(s):  
Marta Stojak ◽  
Magdalena Milczarek ◽  
Anna Kurpinska ◽  
Joanna Suraj-Prazmowska ◽  
Patrycja Kaczara ◽  
...  

Cancer cell cross-talk with the host endothelium plays a crucial role in metastasis, but the underlying mechanisms are still not fully understood. We studied the involvement of protein disulphide isomerase A1 (PDIA1) in human breast cancer cell (MCF-7 and MDA-MB-231) adhesion and transendothelial migration. For comparison, the role of PDIA1 in proliferation, migration, cell cycle and apoptosis was also assessed. Pharmacological inhibitor, bepristat 2a and PDIA1 silencing were used to inhibit PDIA1. Inhibition of PDIA1 by bepristat 2a markedly decreased the adhesion of breast cancer cells to collagen type I, fibronectin and human lung microvascular endothelial cells. Transendothelial migration of breast cancer cells across the endothelial monolayer was also inhibited by bepristat 2a, an effect not associated with changes in ICAM-1 expression or changes in cellular bioenergetics. The silencing of PDIA1 produced less pronounced anti-adhesive effects. However, inhibiting extracellular free thiols by non-penetrating blocker p-chloromercuribenzene sulphonate substantially inhibited adhesion. Using a proteomic approach, we identified that β1 and α2 integrins were the most abundant among all integrins in breast cancer cells as well as in lung microvascular endothelial cells, suggesting that integrins could represent a target for PDIA1. In conclusion, extracellular PDIA1 plays a major role in regulating the adhesion of cancer cells and their transendothelial migration, in addition to regulating cell cycle and caspase 3/7 activation by intracellular PDIA1. PDIA1-dependent regulation of cancer–endothelial cell interactions involves disulphide exchange and most likely integrin activation but is not mediated by the regulation of ICAM-1 expression or changes in cellular bioenergetics in breast cancer or endothelial cells.


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