CD44 splice variants: expression during lymphocyte activation and tumor progression.
A recently described splice variant of CD44 has been shown to confer metastatic potential to non-metastasizing rat pancreatic carcinoma and sarcoma cell lines. Using antibodies raised against a bacterial fusion protein encoded by variant CD44 sequences, we have explored the expression of variant CD44 glycoproteins in human lymphoid cells and tissues, in non-Hodgkin's lymphomas, and in colorectal neoplasia. Normal lymphohematopoietic cells express barely detectable low levels of variant CD44 glycoproteins, while T lymphocytes, upon activation by mitogen or antigen, transiently upregulate expression of specific CD44 variant glycoproteins. The reaction pattern of various antibodies indicates that these CD44 variants contain the domain encoded by exon v6, which is part of the variant that in the rat confers metastatic capability. Interestingly, overexpression of v6 was also found in several aggressive, but not in low-grade, non-Hodgkin's lymphomas (NHL). In human colorectal neoplasia we also observed strong overexpression of CD44 splice variants in all invasive carcinomas and carcinoma metastasis. Interestingly, focal expression was already observed in adenomatous polyps, expression being related to areas of dysplasia. The findings establish CD44 variants as tumor progression markers in colorectal cancer.