scholarly journals Engineering a Vascularized Hypoxic Tumor Model for Therapeutic Assessment

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2201
Author(s):  
Yuta Ando ◽  
Jeong Min Oh ◽  
Winfield Zhao ◽  
Madeleine Tran ◽  
Keyue Shen
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Tumor Angiogenesis ◽  
Tumor Model ◽  
In Vitro Models ◽  
New Device ◽  
Vascular Lumen ◽  
Tumor Section ◽  
Hypoxic Tumor

Solid tumors in advanced cancer often feature a structurally and functionally abnormal vasculature through tumor angiogenesis, which contributes to cancer progression, metastasis, and therapeutic resistances. Hypoxia is considered a major driver of angiogenesis in tumor microenvironments. However, there remains a lack of in vitro models that recapitulate both the vasculature and hypoxia in the same model with physiological resemblance to the tumor microenvironment, while allowing for high-content spatiotemporal analyses for mechanistic studies and therapeutic evaluations. We have previously constructed a hypoxia microdevice that utilizes the metabolism of cancer cells to generate an oxygen gradient in the cancer cell layer as seen in solid tumor sections. Here, we have engineered a new composite microdevice-microfluidics platform that recapitulates a vascularized hypoxic tumor. Endothelial cells were seeded in a collagen channel formed by viscous fingering, to generate a rounded vascular lumen surrounding a hypoxic tumor section composed of cancer cells embedded in a 3-D hydrogel extracellular matrix. We demonstrated that the new device can be used with microscopy-based high-content analyses to track the vascular phenotypes, morphology, and sprouting into the hypoxic tumor section over a 7-day culture, as well as the response to different cancer/stromal cells. We further evaluated the integrity/leakiness of the vascular lumen in molecular delivery, and the potential of the platform to study the movement/trafficking of therapeutic immune cells. Therefore, our new platform can be used as a model for understanding tumor angiogenesis and therapeutic delivery/efficacy in vascularized hypoxic tumors.

scholarly journals Breast Cancer Cells in Microgravity: New Aspects for Cancer Research

2020 ◽  
Vol 21 (19) ◽  
pp. 7345 ◽  
Author(s):  
Mohamed Zakaria Nassef ◽  
Daniela Melnik ◽  
Sascha Kopp ◽  
Jayashree Sahana ◽  
Manfred Infanger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Breast Cancer Cells ◽  
De Novo ◽  
Tumor Model ◽  
Cancer Drug ◽  
Cancer Therapies

Breast cancer is the leading cause of cancer death in females. The incidence has risen dramatically during recent decades. Dismissed as an “unsolved problem of the last century”, breast cancer still represents a health burden with no effective solution identified so far. Microgravity (µg) research might be an unusual method to combat the disease, but cancer biologists decided to harness the power of µg as an exceptional method to increase efficacy and precision of future breast cancer therapies. Numerous studies have indicated that µg has a great impact on cancer cells; by influencing proliferation, survival, and migration, it shifts breast cancer cells toward a less aggressive phenotype. In addition, through the de novo generation of tumor spheroids, µg research provides a reliable in vitro 3D tumor model for preclinical cancer drug development and to study various processes of cancer progression. In summary, µg has become an important tool in understanding and influencing breast cancer biology.

scholarly journals The Circular RNA circXPO1 Promotes Tumor Growth via Sponging MicroRNA-23a in Prostate Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Haoyan Chen ◽  
Ping Zhang ◽  
Bo Yu ◽  
Jinlong Liu
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Tumor Model ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Cancer Tissue ◽  
Pancreatic Cancer Cells ◽  
Malignant Behavior

It has been shown that circular RNA XPO1 (circXPO1) is involved in cancer (e.g., lung adenocarcinoma and osteosarcoma) progression by sponging microRNAs. Nevertheless, the role of circXPO1 and its interaction with microRNAs in prostate cancer remains unknown. In this study, the results of quantitative real-time PCR showed that circXPO1 levels were dramatically increased in human prostate cancer tissue and cell lines compared with those in normal tissue and cell line. Furthermore, cell proliferation, colony formation, and cell invasion assays showed that circXPO1 promoted the malignant behavior of pancreatic cells in vitro. Mechanistically, bioinformatics prediction, a dual-luciferase reporter assay, and pull-down assay suggested that circXPO1 physically targets miR-23a and negatively regulates its expression in pancreatic cancer cells. miR-23a mimics and inhibitors effectively reversed the effects of circXPO1 on the malignant behavior of prostate cancer cells in vitro. Consistent results were observed in the xenograft tumor model. In conclusion, circXPO1 promotes prostate cancer progression via targeting miR-23a, thus suggesting the circXPO1/miR-23a axis can be used as a potential therapeutic target for prostate cancer treatment.

scholarly journals LINC00659 Regulates Colorectal Cancer Migration and Invasion by Targeting miR-485-5p/HOXC13 Axis

2021 ◽  
Author(s):  
Haojie Yang ◽  
Jihong Fu ◽  
Guangyang Jiao ◽  
Yilian Zhu ◽  
Yilin Han ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
In Vitro Models ◽  
Migration And Invasion ◽  
Validation Experiment ◽  
Colorectal Cancer Cells

Abstract BackgroundLong noncoding RNA LINC00659 has been reported to be involved in the carcinogenesis and progression of colorectal cancer. However, the molecular mechanism remains ambiguous.MethodsIn this study, we found that HOXC13 expression was closely related with colorectal cancer and positively correlated with LINC00659 via bioinformatics analysis and clinical validation experiment. Meanwhile, miR-485-5p was identified as an overlapped target miRNA. To further dissect whether miR-485-5p and HOXC13 were involved in LINC00659 mediated colorectal cancer progression, we first established human in vitro models and demonstrated that LINC00659 could directly bind with miR-485-5p and knockdown of LINC00659 upregulated the expression of miR-485-5p. In addition, knockdown of LINC00659 inhibited the expression of HOXC13 by targeting miR-485-5p. Finally, we analyzed the effect of LINC00659/miR-485-5p/HOXC13 axis on tumor growth. Both animal model and in vitro model confirmed the anti-tumor effect of knockdown of LINC00659, which could suppress the colorectal cancer cell viability, migration and invasion by targeting miR-485-5p/HOXC13 axis. Results1. LINC00659 and HOXC13 are highly expressed in colorectal cancer cells.2. miRNA-485-5p is lowly expressed in colorectal cancer cells.3. LINC00659/miR-485-5p/HOXC13 axis is important for colorectal cancer cells.4. LINC00659 promotes tumor growth by sponging miR-485-5p.ConclusionsOur study uncovered a novel mechanism of LINC00659 in the progression of colorectal cancer and provided a potential strategy for the treatment and diagnose of colorectal cancer.

scholarly journals Circular RNA FLNA acts as a sponge of miR-486-3p in promoting lung cancer progression via regulating XRCC1 and CYP1A1

2021 ◽  
Author(s):  
Jiongwei Pan ◽  
Gang Huang ◽  
Zhangyong Yin ◽  
Xiaoping Cai ◽  
Enhui Gong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Lung Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Related Factors

AbstractSignificantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.

scholarly journals POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ronggang Luo ◽  
Yi Zhuo ◽  
Quan Du ◽  
Rendong Xiao
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Cancer Tissues

Abstract Background To detect and investigate the expression of POU domain class 2 transcription factor 2 (POU2F2) in human lung cancer tissues, its role in lung cancer progression, and the potential mechanisms. Methods Immunohistochemical (IHC) assays were conducted to assess the expression of POU2F2 in human lung cancer tissues. Immunoblot assays were performed to assess the expression levels of POU2F2 in human lung cancer tissues and cell lines. CCK-8, colony formation, and transwell-migration/invasion assays were conducted to detect the effects of POU2F2 and AGO1 on the proliferaion and motility of A549 and H1299 cells in vitro. CHIP and luciferase assays were performed for the mechanism study. A tumor xenotransplantation model was used to detect the effects of POU2F2 on tumor growth in vivo. Results We found POU2F2 was highly expressed in human lung cancer tissues and cell lines, and associated with the lung cancer patients’ prognosis and clinical features. POU2F2 promoted the proliferation, and motility of lung cancer cells via targeting AGO1 in vitro. Additionally, POU2F2 promoted tumor growth of lung cancer cells via AGO1 in vivo. Conclusion We found POU2F2 was highly expressed in lung cancer cells and confirmed the involvement of POU2F2 in lung cancer progression, and thought POU2F2 could act as a potential therapeutic target for lung cancer.

scholarly journals Fibroblast activation protein targeted near infrared photoimmunotherapy (NIR PIT) overcomes therapeutic resistance in human esophageal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryoichi Katsube ◽  
Kazuhiro Noma ◽  
Toshiaki Ohara ◽  
Noriyuki Nishiwaki ◽  
Teruki Kobayashi ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Near Infrared ◽  
Fibroblast Activation Protein ◽  
Therapeutic Resistance ◽  
Fibroblast Activation ◽  
Human Esophageal Cancer

AbstractCancer-associated fibroblasts (CAFs) have an important role in the tumor microenvironment. CAFs have the multifunctionality which strongly support cancer progression and the acquisition of therapeutic resistance by cancer cells. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that uses a highly selective monoclonal antibody (mAb)-photosensitizer conjugate. We developed fibroblast activation protein (FAP)-targeted NIR-PIT, in which IR700 was conjugated to a FAP-specific antibody to target CAFs (CAFs-targeted NIR-PIT: CAFs-PIT). Thus, we hypothesized that the control of CAFs could overcome the resistance to conventional chemotherapy in esophageal cancer (EC). In this study, we evaluated whether EC cell acquisition of stronger malignant characteristics and refractoriness to chemoradiotherapy are mediated by CAFs. Next, we assessed whether the resistance could be rescued by eliminating CAF stimulation by CAFs-PIT in vitro and in vivo. Cancer cells acquired chemoradiotherapy resistance via CAF stimulation in vitro and 5-fluorouracil (FU) resistance in CAF-coinoculated tumor models in vivo. CAF stimulation promoted the migration/invasion of cancer cells and a stem-like phenotype in vitro, which were rescued by elimination of CAF stimulation. CAFs-PIT had a highly selective effect on CAFs in vitro. Finally, CAF elimination by CAFs-PIT in vivo demonstrated that the combination of 5-FU and NIR-PIT succeeded in producing 70.9% tumor reduction, while 5-FU alone achieved only 13.3% reduction, suggesting the recovery of 5-FU sensitivity in CAF-rich tumors. In conclusion, CAFs-PIT could overcome therapeutic resistance via CAF elimination. The combined use of novel targeted CAFs-PIT with conventional anticancer treatments can be expected to provide a more effective and sensible treatment strategy.

scholarly journals NR5A2 transcriptional activation by BRD4 promotes pancreatic cancer progression by upregulating GDF15

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Feng Guo ◽  
Yingke Zhou ◽  
Hui Guo ◽  
Dianyun Ren ◽  
Xin Jin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Transcriptional Activation ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Cancer Cells ◽  
Gene Sets ◽  
And Migration

AbstractNR5A2 is a transcription factor regulating the expression of various oncogenes. However, the role of NR5A2 and the specific regulatory mechanism of NR5A2 in pancreatic ductal adenocarcinoma (PDAC) are not thoroughly studied. In our study, Western blotting, real-time PCR, and immunohistochemistry were conducted to assess the expression levels of different molecules. Wound-healing, MTS, colony formation, and transwell assays were employed to evaluate the malignant potential of pancreatic cancer cells. We demonstrated that NR5A2 acted as a negative prognostic biomarker in PDAC. NR5A2 silencing inhibited the proliferation and migration abilities of pancreatic cancer cells in vitro and in vivo. While NR5A2 overexpression markedly promoted both events in vitro. We further identified that NR5A2 was transcriptionally upregulated by BRD4 in pancreatic cancer cells and this was confirmed by Chromatin immunoprecipitation (ChIP) and ChIP-qPCR. Besides, transcriptome RNA sequencing (RNA-Seq) was performed to explore the cancer-promoting effects of NR5A2, we found that GDF15 is a component of multiple down-regulated tumor-promoting gene sets after NR5A2 was silenced. Next, we showed that NR5A2 enhanced the malignancy of pancreatic cancer cells by inducing the transcription of GDF15. Collectively, our findings suggest that NR5A2 expression is induced by BRD4. In turn, NR5A2 activates the transcription of GDF15, promoting pancreatic cancer progression. Therefore, NR5A2 and GDF15 could be promising therapeutic targets in pancreatic cancer.

scholarly journals P2X7 Receptor Promotes Mouse Mammary Cancer Cell Invasiveness and Tumour Progression, and Is a Target for Anticancer Treatment

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2342 ◽  
Author(s):  
Lucie Brisson ◽  
Stéphanie Chadet ◽  
Osbaldo Lopez-Charcas ◽  
Bilel Jelassi ◽  
David Ternant ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
P2x7 Receptor ◽  
Mammary Cancer ◽  
Tumour Progression ◽  
Mammary Cancer Cell ◽  
Cell Invasiveness ◽  
Cancer Cell Invasiveness

The P2X7 receptor is an ATP-gated cation channel with a still ambiguous role in cancer progression, proposed to be either pro- or anti-cancerous, depending on the cancer or cell type in the tumour. Its role in mammary cancer progression is not yet defined. Here, we show that P2X7 receptor is functional in highly aggressive mammary cancer cells, and induces a change in cell morphology with fast F-actin reorganization and formation of filopodia, and promotes cancer cell invasiveness through both 2- and 3-dimensional extracellular matrices in vitro. Furthermore, P2X7 receptor sustains Cdc42 activity and the acquisition of a mesenchymal phenotype. In an immunocompetent mouse mammary cancer model, we reveal that the expression of P2X7 receptor in cancer cells, but not in the host mice, promotes tumour growth and metastasis development, which were reduced by treatment with specific P2X7 antagonists. Our results demonstrate that P2X7 receptor drives mammary tumour progression and represents a pertinent target for mammary cancer treatment.

scholarly journals Twist-mediated PAR1 induction is required for breast cancer progression and metastasis by inhibiting Hippo pathway

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Yifan Wang ◽  
Ruocen Liao ◽  
Xingyu Chen ◽  
Xuhua Ying ◽  
Guanping Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Invasive Breast Cancer ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Hippo Pathway ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition

Abstract Breast cancer is considered to be the most prevalent cancer in women worldwide, and metastasis is the primary cause of death. Protease-activated receptor 1 (PAR1) is a GPCR family member involved in the invasive and metastatic processes of cancer cells. However, the functions and underlying mechanisms of PAR1 in breast cancer remain unclear. In this study, we found that PAR1 is highly expressed in high invasive breast cancer cells, and predicts poor prognosis in ER-negative and high-grade breast cancer patients. Mechanistically, Twist transcriptionally induces PAR1 expression, leading to inhibition of Hippo pathway and activation of YAP/TAZ; Inhibition of PAR1 suppresses YAP/TAZ-induced epithelial-mesenchymal transition (EMT), invasion, migration, cancer stem cell (CSC)-like properties, tumor growth and metastasis of breast cancer cells in vitro and in vivo. These findings suggest that PAR1 acts as a direct transcriptionally target of Twist, can promote EMT, tumorigenicity and metastasis by controlling the Hippo pathway; this may lead to a potential therapeutic target for treating invasive breast cancer.

Sign in / Sign up

Export Citation Format

Share Document