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Article

Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue

1
Departamento de Biología del Cáncer, Instituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), 28029 Madrid, Spain
2
Instituto de Investigación del Hospital Universitario La Paz (IdiPAZ), 28029 Madrid, Spain
3
Centro de Investigaciones Biomédicas en Red-Cáncer (CIBERONC), 28029 Madrid, Spain
4
Unidad de Genómica, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain
5
Departamento de Patología, Hospital Universitario La Paz, 28029 Madrid, Spain
6
Unidad Colorrectal, Departamento de Cirugía, Hospital Universitario La Paz, 28029 Madrid, Spain
7
Centro de Investigaciones Biomédicas en Red-Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain
8
Unidad de Endoscopia, Departamento de Digestivo, Hospital Universitario La Paz, 28029 Madrid, Spain
*
Author to whom correspondence should be addressed.
These authors contributed equally as Co-Last.
Cancers 2020, 12(8), 2302; https://doi.org/10.3390/cancers12082302
Received: 24 July 2020 / Revised: 7 August 2020 / Accepted: 13 August 2020 / Published: 15 August 2020
(This article belongs to the Special Issue Stemness and Differentiation in Cancer)
Colon and rectal tumors, often referred to as colorectal cancer, show different gene expression patterns in studies that analyze whole tissue biopsies containing a mix of tumor and non-tumor cells. To better characterize colon and rectal tumors, we investigated the gene expression profile of organoids generated from endoscopic biopsies of rectal tumors and adjacent normal colon and rectum mucosa from therapy-naive rectal cancer patients. We also studied the effect of vitamin D on these organoid types. Gene profiling was performed by RNA-sequencing. Organoids from a normal colon and rectum had a shared gene expression profile that profoundly differed from that of rectal tumor organoids. We identified a group of genes of the biosynthetic machinery as rectal tumor organoid-specific, including those encoding the RNA polymerase II subunits POLR2H and POLR2J. The active vitamin D metabolite 1α,25-dihydroxyvitamin D3/calcitriol upregulated stemness-related genes (LGR5, LRIG1, SMOC2, and MSI1) in normal rectum organoids, while it downregulated differentiation marker genes (TFF2 and MUC2). Normal colon and rectum organoids share similar gene expression patterns and respond similarly to calcitriol. Rectal tumor organoids display distinct and heterogeneous gene expression profiles, with differences with respect to those of colon tumor organoids, and respond differently to calcitriol than normal rectum organoids. View Full-Text
Keywords: colorectal cancer; stem cells; patient-derived organoids; rectal tumors; vitamin D colorectal cancer; stem cells; patient-derived organoids; rectal tumors; vitamin D
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MDPI and ACS Style

Costales-Carrera, A.; Fernández-Barral, A.; Bustamante-Madrid, P.; Domínguez, O.; Guerra-Pastrián, L.; Cantero, R.; del Peso, L.; Burgos, A.; Barbáchano, A.; Muñoz, A. Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue. Cancers 2020, 12, 2302. https://doi.org/10.3390/cancers12082302

AMA Style

Costales-Carrera A, Fernández-Barral A, Bustamante-Madrid P, Domínguez O, Guerra-Pastrián L, Cantero R, del Peso L, Burgos A, Barbáchano A, Muñoz A. Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue. Cancers. 2020; 12(8):2302. https://doi.org/10.3390/cancers12082302

Chicago/Turabian Style

Costales-Carrera, Alba, Asunción Fernández-Barral, Pilar Bustamante-Madrid, Orlando Domínguez, Laura Guerra-Pastrián, Ramón Cantero, Luis del Peso, Aurora Burgos, Antonio Barbáchano, and Alberto Muñoz. 2020. "Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue" Cancers 12, no. 8: 2302. https://doi.org/10.3390/cancers12082302

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