Olfactomedin 4 associates with expression of differentiation markers but not with properties of cancer stemness, EMT nor metastatic spread in colorectal cancer.

Abstract

Tumor stem cells play a pivotal role in carcinogenesis and metastatic spread in colorectal cancer (CRC). Olfactomedin 4 (OLFM4) is co-expressed with the established stem cell marker leucine-rich repeat-containing G protein-coupled receptor 5 at the bottom of intestinal crypts and has been suggested as a surrogate for cancer stemness and a biomarker in gastrointestinal tumors associated with prognosis. Therefore, it was the aim of the present study to clarify whether OLFM4 is involved in carcinogenesis and metastatic spread in CRC. We used a combined approach of functional assays using forced OLFM4 overexpression in human CRC cell lines, xenograft mice, and an immunohistochemical approach using patient tissues to investigate the impact of OLFM4 on stemness, canonical Wnt signaling, properties of metastasis and differentiation as well as prognosis. OLFM4 expression correlated weakly with tumor grade in one patient cohort (metastasis collection: p = 0.05; pooled analysis of metastasis collection and survival collection: p = 0.19) and paralleled the expression of differentiation markers (FABP2, MUC2, and CK20) (p = 0.002) but did not correlate with stemness-associated markers. Further analyses in CRC cells lines as well as xenograft mice including forced overexpression of OLFM4 revealed that OLFM4 neither altered the expression of markers of stemness nor epithelial-mesenchymal transition, nor did OLFM4 itself drive proliferation, migration, or colony formation, which are all prerequisites of carcinogenesis and tumor progression. In line with this, we found no significant correlation between OLFM4 expression, metastasis, and patient survival. In summary, expression of OLFM4 in human CRC seems to be characteristic of differentiation marker expression in CRC but is not a driver of carcinogenesis nor metastatic spread.

• Authors: Stefanie Jaitner, Elise Pretzsch, Jens Neumann, Achim Schäffauer, Matthias Schiemann, Martin Angele, Jörg Kumbrink, Sarah Schwitalla, Florian R Greten, Lydia Brandl, Frederick Klauschen, David Horst, Thomas Kirchner, Andreas Jung
• Journal: The journal of pathology. Clinical research (J Pathol Clin Res) Vol. 9 Issue 1 Pg. 73-85 (01 2023) ISSN: 2056-4538 [Electronic] England
• PMID: 36349502 (Publication Type: Journal Article)
• Copyright: © 2022 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.

Chemical References

• Antigens, Differentiation
• Granulocyte Colony-Stimulating Factor
• OLFM4 protein, human

Topics

• Animals
• Humans
• Mice
• Antigens, Differentiation (genetics, metabolism)
• Colorectal Neoplasms (genetics, metabolism)
• Epithelial-Mesenchymal Transition (genetics)
• Granulocyte Colony-Stimulating Factor (genetics, metabolism)
• Neoplastic Stem Cells (metabolism)