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.
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.
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.
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.
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.
Increased and disorganised expression of CD44 variant exons has been demonstrated in biopsy samples of several types of human malignancy by many groups.
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.
In recent years, the measurement of soluble CD44 levels in the circulation of patients with malignant diseases has been introduced as a new and simple diagnostic tool for the detection of human cancer.
In order to test this postulate, the expression of three important CAMs involved in tumor processes (CD44, ICAM-1 and LFA-3) in the human cancer cell lines HT29 (colon adenocarcinoma), A431 (squamous epidermal carcinoma) and A2780 (ovarian carcinoma) grown in monolayer or as multicellular spheroids was compared.
Adenocarcinomas, including primary and metastatic lesions, or cancer cell lines of the stomach revealed consistently very low or undetectable levels of expression of exon v6 of the CD44 variant (CD44v) protein.
The mean (SD) fractions of positively stained cancer cells were 38 (38), 10 (22), 56 (41) and 93% (17) for CD44s, CD44v3, CD44v6 and alpha-catenin, respectively.
In normal colonic mucosa, the expression of CD44 variants are low but in cancer tissue and its regional lymph node, the expression of CD44V and CD44V6/7 were significantly higher and more frequent than any other CD44 variants (p<0.05).
We found a deregulation in the CD44 expression pattern in malignant tumors of both type of cancer compared with the one in benign tumors or normal tissue.