Expression of the cell surface glycoprotein CD44/Pgp-1, which mediates cell-substrate interactions is increased in many types of malignancies, but the role of CD44 in tumor growth is largely undefined.
This report presents evidence that an abnormal pattern of activity of the CD44 gene is a promising candidate for both of these purposes in various types of malignancy.
In conclusion, epitopes on exon v6 and constant part of CD44 are differentially synthesized and regulated during normal and malignant growth of cells in man.
The correlation between CD44 and the non-small cell phenotype was further demonstrated in studies of a cultured small cell lung cancer line induced to exhibit characteristics of a non-small lung cancer by infection with v-Ha-ras.
Unusual activity of the CD44 locus in neoplasia and malignancy is confirmed, and techniques for the analysis of such activity can enable non-invasive investigation of patients for primary or recurrent bladder cancer or for other tumours that shed neoplastic cells into body fluids.
Furthermore, lymph-vascular space involvement of cancer cells was observed to be statistically significant in the CD44-negative group as opposed to the positive group.
Increased and disorganised expression of CD44 variant exons has been demonstrated in biopsy samples of several types of human malignancy by many groups.
Aberrant expression of the cell adhesion molecule CD44 has been detected in human tumors and the expression of specific CD44 isoforms (splice variants) has been shown to be associated with metastasis and poor prognosis in human malignancies.
Beside cell-surface expression, the measurement of soluble CD44 in serum of cancer patients could be useful in early diagnosis and assessment of disease status.
The expression of specific cell adhesion molecule CD44 isoforms (splice variants) has been shown to be associated with poor prognosis in human malignancies, such as breast cancer.
The variants of CD44 resulting from variable exon splicing are found in metastasizing human malignancies and are also involved in hyaluronan uptake and degradation.
Among the probes generated, the CD44 intron 9 probe was the best for distinguishing cancer tissue from normal tissue in adenocarcinomas of the colorectum or stomach.
We conclude that the development of methods for the accurate quantitation of over-abundant CD44 RNA species in clinical samples offers the most promising approach to improved early diagnosis of malignancy using this new marker.
These observations demonstrate that the unusual variety of CD44 transcripts in cancer cells results from the fidelity of alternative splicing mechanisms being compromised and are potentially useful as tumor cell markers in diagnostic assays.
Overexpression of discrete CD44 isoforms containing products of variant exons have been implicated in the progression of cancer, including human colon carcinoma.
The role of CD44 in neoplasia is less well defined, although metastatic potential can be conferred on non-metastasising cell lines by transfection with a variant of CD44 and high levels of CD44 are associated with several types of malignant tumours.