However, it is clear that, as with the abnormal expression pattern of CD44 variant exons, intron 9 retention is a good-candidate molecular diagnostic tool for colorectal carcinomas.
These findings indicated that this domain of the CD44 glycoprotein encoded by exons v8-10 may play an important role in tumor hematogenous metastasis of human colorectal cancer.
CD44 exon variant 6 epitope and hyaluronate synthase are expressed on HT29 human colorectal carcinoma cells in a SCID mouse model of metastasis formation.
The expression of CD44-mRNA was examined in 90 specimens from 44 patients with colorectal cancer or colorectal adenomatous polyps and in the peripheral blood leukocytes from 7 healthy volunteers by reverse transcription-polymerase chain reaction and Southern blot hybridization.
Abnormal expression of the variant exons and of intron 9 of the CD44 gene in tumour cells exfoliated into the colonic lumen may be helpful markers for the early, non-invasive, diagnosis of colorectal cancer.
The overexpression of such abnormal CD44 variants was observed from an early stage in colorectal cancer and did not correlate with nodal or distant metastatic status.
Using a new set of primers for exon-specific reverse transcription-polymerase chain reaction (RT-PCR) we delineated the exact exon composition of CD44 mRNAs in normal colorectal mucosa, including isolated colonic crypts, in colorectal carcinomas and in their hepatic metastases.
Multivariate analysis demonstrated that CD44 expression and lymph node metastasis in gastric cancer and CD44 and sialyl Lea expression in colorectal cancer were significantly related to hepatic metastasis.
Based on the important role of CD44 splice variants in colorectal cancer progression and metastasis, we evaluated the use of CD44v6 expression to detect and assess the metastatic potential of colorectal tumour cells circulating in peripheral blood.
The current results suggest that the up-regulation of CD44 variant 6 through nuclear beta-catenin activation may contribute to the formation of tumor budding, and immunostaining of these two adhesion molecules may be useful in identifying those at high-risk for locoregional failure among patients with T1 colorectal carcinoma.
This study is the first to demonstrate the mitigating effect of CD44s expression on the hepatic metastatic phenotype in a colorectal carcinoma cell line that does not ordinarily express CD44.