The recent discoveries concerning the genetics of human apomucins which are presented in the article of J.P. Aubert et N. Porchet will profoundly modify in the near future our understanding of the role of mucins in digestive pathology. This perturbation has already been observed in cancer research and in chronic inflammatory intestinal disease (CIID).
IN CANCER RESEARCH
A first example of the application of the MUC genes was furnished by villous tumors. These are characterized by an abundant mucosecretion and an elevated risk of transformation and recurrence. In the work based on 22 rectosigmoidal villous tumors, we observed a constant overexpression of the MUC 2 gene as well as an aberrant expression of the MUC 5AC gene which was never expressed in healthy colon mucosa. This aberrant expression was very strong when the tumor exhibited low grade dysplasia, diminished with the grade of dysplasia and disappeared when an adenoma is transformed into an adenocarcinoma.
MUC 5 AC gene was not expressed in colon adenocarcinomas without a precedent of villous tumor. Also its expression could be an early marker of villous tumor transformation. In addition, in 20% of the cases, there exists a positive marker of MUC 5AC at a distance from the tumor, in the endoscopically and histologically nomal zones. Several prospective studies are now necessary to know if this aberrent expression may or may not be an early marker of tumor recurrence.
CIID
No single pathogenic agent has been identified in CIID. Nevertheless, there exists a number of experimental arguments in favor of an inductor and stimulator role for bacteria of the saprophyte endogenous flora in intestinal inflammation. The colonization of intestinal lesions of CIID (ulcers and fistulas) principally by the germs of the E. Coli type and strepococcus, increases of bacteria translocation induction of experimental colitis by fragments of bacterial walls formylated oligopeptides, peptidoglycans-polysaccharides (PG-PS), lesions of less severe character of experimental colitis secondary to administration of indomethacin in germ-free animals compared with control animals, aggravation of this colitis by PG-PS and amelioration by antibiotics with a large spectrum. The work of P. Rutgeerts on the endoscopic recurrent model of Crohn's disease (CD) following surgery equally suggested that the bacterial flora may play an important role in a re-activation of the disease.
As indicated in the previous issue of Mucus Dialogue, the mucus is one mean of defence by the intestinal mucosa against environmental agents. Several quantitative and/or qualitative variations of mucus can render the mucosa more vulnerable to the penetration of endoluminal agents and therefore favor a chronic inflammatory reaction in CIID.
The quantitative aspect was recently appraized by the measure of mucus thickness: it was not existant in Ulcerative Colitis (UC) in the ulcerated zone but was increased in CD.
The qualitative anomalies identified to date are based on the glycan moieties of the mucins :
CONCLUSION
Further work will now be necessary to allow a better understanding of the function of the different mucin genes and the mechanisms responsible for activation and/or deactivation of their expression.