Organoids Are Limited in Modeling the Colon Adenoma-Carcinoma Sequence

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2021 Mar 6

PMID 33668713

Citations 12

Authors

Yoshihisa Tokumaru

Masanori Oshi

Ankit Patel

Wanqing Tian

Li Yan

Nobuhisa Matsuhashi

Manabu Futamura

Kazuhiro Yoshida

Kazuaki Takabe

Affiliations

Soon will be listed here.

Abstract

The colon adenoma-carcinoma sequence is a multistep genomic-altering process that occurs during colorectal cancer (CRC) carcinogenesis. Organoids are now commonly used to model both non-cancerous and cancerous tissue. This study aims to investigate how well organoids mimic tissues in the adenoma-carcinoma sequence by comparing their transcriptomes. A total of 234 tissue samples (48 adenomas and 186 CRC) and 60 organoid samples (15 adenomas and 45 CRC) were analyzed. We found that cell-proliferation-related gene sets were consistently enriched in both CRC tissues and organoids compared to adenoma tissues and organoids by gene set enrichment analysis (GSEA). None of the known pathways in the colon adenoma-carcinoma sequence were consistently enriched in CRC organoids. There was no enrichment of the tumor microenvironment-related gene sets in CRC organoids. CRC tissues enriched immune-response-related gene sets, whereas CRC organoids did not. The proportions of infiltrating immune cells were different between tissues and organoids, whereas there was no difference between cancer and adenoma organoids. The amounts of cancer stem cells and progenitor cells were not different between CRC and adenoma organoids, whereas a difference was noted between CRC and adenoma tissues. In conclusion, we demonstrated that organoids model only part of the adenoma-carcinoma sequence and should be used with caution after considering their limitations.

Citing Articles

Signaling pathways in colorectal cancer implications for the target therapies.

Song Y, Chen M, Wei Y, Ma X, Shi H Mol Biomed. 2024; 5(1):21.

PMID: 38844562 PMC: 11156834. DOI: 10.1186/s43556-024-00178-y.

The Role of the Microbiome on the Pathogenesis and Treatment of Colorectal Cancer.

Yu I, Wu R, Tokumaru Y, Terracina K, Takabe K Cancers (Basel). 2022; 14(22).

PMID: 36428777 PMC: 9688177. DOI: 10.3390/cancers14225685.

Higher intra-tumoral expression of pro-coagulation genes is a predictor of angiogenesis, epithelial mesenchymal transition and worse patient survival in gastric cancer.

Oshi M, Sarkar J, Tokumaru Y, Yan L, Kosaka T, Akiyama H Am J Cancer Res. 2022; 12(8):4001-4014.

PMID: 36119815 PMC: 9442006.

Intratumoral lymphatic endothelial cell infiltration reflecting lymphangiogenesis is counterbalanced by immune responses and better cancer biology in the breast cancer tumor microenvironment.

Wu R, Sarkar J, Tokumaru Y, Takabe Y, Oshi M, Asaoka M Am J Cancer Res. 2022; 12(2):504-520.

PMID: 35261783 PMC: 8899974.

Low RUFY3 expression level is associated with lymph node metastasis in older women with invasive breast cancer.

Angarita F, Oshi M, Yamada A, Yan L, Matsuyama R, Edge S Breast Cancer Res Treat. 2022; 192(1):19-32.

PMID: 35018543 PMC: 8844209. DOI: 10.1007/s10549-021-06482-3.

References

Newman A, Steen C, Liu C, Gentles A, Chaudhuri A, Scherer F . Determining cell type abundance and expression from bulk tissues with digital cytometry. Nat Biotechnol. 2019; 37(7):773-782. PMC: 6610714. DOI: 10.1038/s41587-019-0114-2. View

MORSON B . Evolution of cancer of the colon and rectum. Cancer. 1974; 34(3):suppl:845-9. DOI: 10.1002/1097-0142(197409)34:3+<845::aid-cncr2820340710>3.0.co;2-h. View

Joharatnam-Hogan N, Wilson W, Shiu K, Fusai G, Davidson B, Hochhauser D . Multimodal Treatment in Metastatic Colorectal Cancer (mCRC) Improves Outcomes-The University College London Hospital (UCLH) Experience. Cancers (Basel). 2020; 12(12). PMC: 7760146. DOI: 10.3390/cancers12123545. View

Oshi M, Asaoka M, Tokumaru Y, Yan L, Matsuyama R, Ishikawa T . CD8 T Cell Score as a Prognostic Biomarker for Triple Negative Breast Cancer. Int J Mol Sci. 2020; 21(18). PMC: 7555570. DOI: 10.3390/ijms21186968. View

Weeber F, Ooft S, Dijkstra K, Voest E . Tumor Organoids as a Pre-clinical Cancer Model for Drug Discovery. Cell Chem Biol. 2017; 24(9):1092-1100. DOI: 10.1016/j.chembiol.2017.06.012. View

van de Wetering M, Francies H, Francis J, Bounova G, Iorio F, Pronk A . Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell. 2015; 161(4):933-45. PMC: 6428276. DOI: 10.1016/j.cell.2015.03.053. View

Lancaster M, Knoblich J . Organogenesis in a dish: modeling development and disease using organoid technologies. Science. 2014; 345(6194):1247125. DOI: 10.1126/science.1247125. View

Oshi M, Newman S, Tokumaru Y, Yan L, Matsuyama R, Kalinski P . Plasmacytoid Dendritic Cell (pDC) Infiltration Correlate with Tumor Infiltrating Lymphocytes, Cancer Immunity, and Better Survival in Triple Negative Breast Cancer (TNBC) More Strongly than Conventional Dendritic Cell (cDC). Cancers (Basel). 2020; 12(11). PMC: 7697894. DOI: 10.3390/cancers12113342. View

Xu H, Lyu X, Yi M, Zhao W, Song Y, Wu K . Organoid technology and applications in cancer research. J Hematol Oncol. 2018; 11(1):116. PMC: 6139148. DOI: 10.1186/s13045-018-0662-9. View

10.

Katsuta E, Rashid O, Takabe K . Murine breast cancer mastectomy model that predicts patient outcomes for drug development. J Surg Res. 2017; 219:310-318. PMC: 5675042. DOI: 10.1016/j.jss.2017.06.048. View

11.

Oshi M, Newman S, Murthy V, Tokumaru Y, Yan L, Matsuyama R . ITPKC as a Prognostic and Predictive Biomarker of Neoadjuvant Chemotherapy for Triple Negative Breast Cancer. Cancers (Basel). 2020; 12(10). PMC: 7601042. DOI: 10.3390/cancers12102758. View

12.

Tokumaru Y, Oshi M, Katsuta E, Yan L, Huang J, Nagahashi M . Intratumoral Adipocyte-High Breast Cancer Enrich for Metastatic and Inflammation-Related Pathways but Associated with Less Cancer Cell Proliferation. Int J Mol Sci. 2020; 21(16). PMC: 7461211. DOI: 10.3390/ijms21165744. View

13.

Oshi M, Tokumaru Y, Asaoka M, Yan L, Satyananda V, Matsuyama R . M1 Macrophage and M1/M2 ratio defined by transcriptomic signatures resemble only part of their conventional clinical characteristics in breast cancer. Sci Rep. 2020; 10(1):16554. PMC: 7538579. DOI: 10.1038/s41598-020-73624-w. View

14.

Lau H, Kranenburg O, Xiao H, Yu J . Organoid models of gastrointestinal cancers in basic and translational research. Nat Rev Gastroenterol Hepatol. 2020; 17(4):203-222. DOI: 10.1038/s41575-019-0255-2. View

15.

McMillin D, Negri J, Mitsiades C . The role of tumour-stromal interactions in modifying drug response: challenges and opportunities. Nat Rev Drug Discov. 2013; 12(3):217-28. DOI: 10.1038/nrd3870. View

16.

Kawaguchi T, Foster B, Young J, Takabe K . Current Update of Patient-Derived Xenograft Model for Translational Breast Cancer Research. J Mammary Gland Biol Neoplasia. 2017; 22(2):131-139. PMC: 5511343. DOI: 10.1007/s10911-017-9378-7. View

17.

Oshi M, Takahashi H, Tokumaru Y, Yan L, Rashid O, Matsuyama R . G2M Cell Cycle Pathway Score as a Prognostic Biomarker of Metastasis in Estrogen Receptor (ER)-Positive Breast Cancer. Int J Mol Sci. 2020; 21(8). PMC: 7215898. DOI: 10.3390/ijms21082921. View

18.

Rashid O, Nagahashi M, Ramachandran S, Dumur C, Schaum J, Yamada A . An improved syngeneic orthotopic murine model of human breast cancer progression. Breast Cancer Res Treat. 2014; 147(3):501-12. PMC: 4176514. DOI: 10.1007/s10549-014-3118-0. View

19.

Subramanian A, Tamayo P, Mootha V, Mukherjee S, Ebert B, Gillette M . Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102(43):15545-50. PMC: 1239896. DOI: 10.1073/pnas.0506580102. View

20.

Barbie D, Tamayo P, Boehm J, Kim S, Moody S, Dunn I . Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature. 2009; 462(7269):108-12. PMC: 2783335. DOI: 10.1038/nature08460. View