scholarly journals Revisiting colorectal cancer tumorigenesis with spatially-resolved gene expression profiling

2021 ◽  
Author(s):  
Jessica Roelands ◽  
Manon van der Ploeg ◽  
Hao Dang ◽  
Jurjen J. Boonstra ◽  
James C.H. Hardwick ◽  
...  

Early detection and treatment are paramount to the clinical outcome of patients with colorectal cancer (CRC). Deciphering the dynamic interactions that occur between epithelial cells and stromal cells during tumorigenesis requires in-depth analyses of early-stage CRC lesions in spatial context. Here we employed spatially-resolved gene expression profiling to dissect molecular processes that associate with malignant transformation in CRC. We provide the transcriptional landscapes of colorectal cancer tumorigenesis from healthy mucosa, through different degrees of dysplasia, to cancer. The complementary examination of epithelial and stromal fractions allowed us to define whether specific oncogenic processes involved cancer cells, stromal cells, or the tumor microenvironment as a whole. We identified several genes that were consistently deregulated during CRC onset that could serve as clinical biomarkers for early-stage CRC. Furthermore, we uncovered an essential role for the innate immune system during CRC tumorigenesis.

2014 ◽  
Author(s):  
Yann Gaston-Mathé ◽  
CHARLES FERTE ◽  
benoit gauthier ◽  
mathilde bateson ◽  
david planchard ◽  
...  

2015 ◽  
Author(s):  
Hiroaki Niitsu ◽  
Takao Hinoi ◽  
Yasuo Kawaguchi ◽  
Kazuhiro Sentani ◽  
Naohide Oue ◽  
...  

2013 ◽  
Vol 30 (2) ◽  
Author(s):  
Irene Guijarro-Muñoz ◽  
Antonio Sánchez ◽  
Esther Martínez-Martínez ◽  
Jose M. García ◽  
Clara Salas ◽  
...  

2011 ◽  
Vol 300 (1) ◽  
pp. F177-F188 ◽  
Author(s):  
Masanori Kugita ◽  
Kazuhiro Nishii ◽  
Miwa Morita ◽  
Daisuke Yoshihara ◽  
Hiroe Kowa-Sugiyama ◽  
...  

Han:SPRD Cy is a spontaneous rat model of polycystic kidney disease (PKD) caused by a missense mutation in Pkdr1. Cystogenesis in this model is not clearly understood. In the current study, we performed global gene expression profiling in early-stage PKD cyst development in Cy/Cy kidneys and normal (+/+) kidneys at 3 and 7 days of postnatal age. Expression profiles were determined by microarray analysis, followed by validation with real-time RT-PCR. Genes were selected with over 1.5-fold expression changes compared with age-matched +/+ kidneys for canonical pathway analysis. We found nine pathways in common between 3- and 7-day Cy/Cy kidneys. Three significantly changed pathways were designated “Vitamin D Receptor (VDR)/Retinoid X Receptor (RXR) Activation,” “LPS/IL-1-Mediated Inhibition of RXR Function,” and “Liver X Receptor (LXR)/RXR Activation.” These results suggest that RXR-mediated signaling is significantly altered in developing kidneys with mutated Pkdr1. In gene ontology analysis, the functions of these RXR-related genes were found to be involved in regulating cell proliferation and organ morphogenesis. With real-time RT-PCR analysis, the upregulation of Ptx2, Alox15b, OSP, and PCNA, major markers of cell proliferation associated with the RXR pathway, were confirmed in 3- and 7-day Cy/Cy kidneys compared with 3-day +/+ kidneys. The increased RXR protein was observed in both the nucleus and cytoplasm of cystic epithelial cells in early-stage Cy/Cy kidneys, and the RXR-positive cells were strongly positive for PCNA staining. Taken together, cell proliferation and organ morphogenesis signals transduced by RXR-mediated pathways may have important roles for cystogenesis in early-stage PKD in this Pkdr1-mutated Cy rat.


Sign in / Sign up

Export Citation Format

Share Document