Oncotarget

Research Papers:

Loss of DRO1/CCDC80 in the tumor microenvironment promotes carcinogenesis

Jessica I. Christian _, Agnieszka Pastula, Andreas Herbst, Jens Neumann, Maximilian K. Marschall, Andrea Ofner, Heike Zierahn, Marlon R. Schneider, Eckhard Wolf, Michael Quante and Frank T. Kolligs

PDF  |  Full Text  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2021. [Epub ahead of print] https://doi.org/10.18632/oncotarget.28084

Metrics: PDF 49 views  |   Full Text 217 views  |   ?  


Abstract

Jessica I. Christian1,*, Agnieszka Pastula2,*, Andreas Herbst3,4, Jens Neumann5, Maximilian K. Marschall1, Andrea Ofner3, Heike Zierahn1, Marlon R. Schneider1, Eckhard Wolf1, Michael Quante2 and Frank T. Kolligs3,6,7,8

1 Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig Maximilian University of Munich, 81377 Munich, Germany

2 Gastroenterologie II, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany

3 Department of Medicine II, Ludwig Maximilian University of Munich, 81377 Munich, Germany

4 Institute of Laboratory Medicine, University Hospital, Ludwig Maximilian University of Munich, 81377 Munich, Germany

5 Institute of Pathology, Ludwig Maximilian University of Munich, 80337 Munich, Germany

6 German Cancer Consortium (DKTK), 69120 Heidelberg, Germany

7 German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany

8 Department of Internal Medicine and Gastroenterology, HELIOS Klinikum Berlin-Buch, 13125 Berlin, Germany

* These authors contributed equally to this work

Correspondence to:

Jessica I. Christian, email: christian@genzentrum.lmu.de

Keywords: DRO1; CCDC80; colorectal cancer; tumor microenvironment; tumor suppressor

Received: July 09, 2021     Accepted: September 04, 2021     Published: PUBLISHED_DATE

Copyright: © 2021 Christian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Tumors are composed of the tumor cells and the surrounding microenvironment. Both are closely interwoven and interact by a complex and multifaceted cross-talk which plays an integral part in tumor initiation, growth, and progression. Dro1/Ccdc80 has been shown to be a potent suppressor of colorectal cancer and ubiquitous inactivation of Dro1/Ccdc80 strongly promoted colorectal carcinogenesis in ApcMin/+ mice and in a chemically-induced colorectal cancer model.

The aim of the present study was to investigate whether Dro1/Ccdc80’s tumor suppressive function is tumor-cell-autonomous. Expression of Dro1/Ccdc80 in cancer cells had no effect on both colon tumor development in ApcMin/+ mice and formation of xenograft tumors. In contrast, DRO1/CCDC80 loss in the microenvironment strongly increased tumor growth in xenograft models, inhibited cancer cell apoptosis, and promoted intestinal epithelial cell migration. Moreover, stromal Dro1/Ccdc80 inactivation facilitated formation of intestinal epithelial organoids. Expression analyses showed Dro1/Ccdc80 to be significantly down-regulated in murine gastric cancer associated fibroblasts, in ApcMin/+ colon tumor primary stromal cells and in microdissected stroma from human colorectal cancer compared to normal, non-tumor stroma. Our results demonstrate epithelial derived DRO1/CCDC80 to be dispensable for intestinal tissue homeostasis and identify Dro1/Ccdc80 as tumor suppressor in the tumor microenvironment.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 28084