Modifier-concept of colorectal carcinogenesis: lipidomics as a technical tool in pathway analysis

Abstract

In the modifier concept of intestinal carcinogenesis, lipids have been established as important variables and one focus is given to long-chain fatty acids. Increased consumption of long-chain fatty acids is in discussion to modify the development of colorectal carcinoma in humans. Saturated long-chain fatty acids, in particular, are assumed to promote carcinogenesis, whereas polyunsaturated forms are likely to act in the opposite way. At present, the molecular mechanisms behind these effects are not well understood. Recently, it has been demonstrated by lipidomics and associated molecular techniques, that activation and metabolic channeling of long-chain fatty acids are important mechanisms to modify colorectal carcinogenesis. In this Editorial, an overview about the present concept of long-chain fatty acids and its derivatives in colorectal carcinogenesis as well as technical algorithms in lipid analysis is given.

Keywords: Acyl-CoA; Carcinogenesis; Colorectal neoplasms; Lipidomics; Long-chain fatty acids.

Figure 1

The modifier concept of colorectal carcinogenesis. The important key points in enterocytic life span, proliferation and apoptosis, are connected by basal molecular pathways. Such pathways, as well as cell behavior determining molecular entities such as the genome, transcriptome, proteome, metabolome, and lipidome, are exposed to cellular stress and act as modifiers. In addition to enterocytes, the intestinal stem cells are affected by this evolutionary principle. The aberrant modification of pathways is suggested as an important variable in colorectal carcinogenesis. The term nutrigenome of tumor cells reflects the genome modification of malignant cells by dietary components with expression of so-called modifier genes as demonstrated in APC mice.

Figure 2

Summary of the lipidomics work flow - lipid extraction and analysis. TLC: Thin layer chromatography; GC: Gas chromatography; HPLC: High pressure liquid chromatography; ESI: Electrospray ionization; MALDI-TOF: Matrix-assisted laser desorption ionization-time-of flight.