The presence of high levels of CD44 on malignant cells could increase the ability of these cells to adhere to matrix proteins and/or to interact with endothelium, thus potentially altering their capacity for invasiveness and metastasis.
To investigate if human tumours display altered CD44 expression we performed reverse transcriptase a polymerase chain reaction (PCR) analysis of CD44 in 49 specimens from normal colonic mucosa, primary colon and rectal tumours, normal liver, and metastases of 20 patients.
The finding that metastasis-related variants are already expressed at a relatively early stage in colorectal carcinogenesis and tumor progression, i.e., in adenomatous polyps, suggests the existence of a yet unknown selective advantage linked to CD44 variant expression.
CD44 is a cell-surface glycoprotein postulated to play a role in a variety of biological processes, including lymphocyte homing and tumor-cell metastasis.
CD44 expression, observed in only 49% of primary tumours, was associated with distant metastases at time of diagnosis and, among 31 curatively resected patients, with tumour recurrence (p = 0.0014) and increased mortality (p = 0.001) during follow-up averaging 17 months.
These results suggest that CD44 could play important roles in the function of normal endometrium and that reduced CD44 expression might be related to the metastasis of endometrial cancer cells through lymph-vascular space.
Furthermore, in endocrine pancreatic tumors with metastatic disease, CD44-positive tumors had a tendency to metastasize to lymph nodes (P = 0.005), as compared with CD44-negative tumors which were locally invasive or metastasized to the liver.
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.
Normal urothelium, well to moderately differentiated cell lines and surgical samples expressed E-cadherin and large CD44 isoforms containing exon v6, which was pivotal in metastasis of rat pancreatic cell line model.
Insignificant differences in activity of CD 34 in various pathologies, up-regulation of CD 44 in poorly differentiated HCC and down-regulation in metastatic tumors were found.
Recently expression of some alternatively-spliced variants of CD44 transcripts (CD44v) has been suggested to play a potential role in tumor metastasis and the detection of CD44v containing exon 6 to 11 may be helpful for the diagnosis of cancers.
In all normal brain and tumor samples, with the exception ofmetastases from colon carcinoma, PCR analysis demonstrated one prominent product that corresponded to the CD44H hematopoietic form of CD44.
Most importantly, a neutralizing antibody to CD44 inhibited cell proliferation and basement membrane invasive activity, suggesting a definitive role of CD44 in prostate tumor growth and metastasis.
Expression of CD44, particularly of certain splice variants, has been linked to tumor progression and metastasis formation in a number of different animal and human cancers.
The relation between expression of several splicing variants of the CD 44 glycoprotein by tumor cells and the increased risk of metastases was discussed recently.
To examine whether renal cell carcinoma displays altered CD44 expression we performed reverse transcription-polymerase chain reaction (RT-PCR) analysis of CD44 in 38 specimens from renal cancer, normal kidney and metastases of 19 patients and 6 renal cancer cell lines.
When it was noted in a rat tumor model that the transfer of cDNA of a single gene, a CD44 variant isoform (CD44v) covering the exons v4-v7, sufficed to initiate metastasis formation of a locally growing tumor, hope was created that a "metastogene" may have been identified.