Activated human lymphocytes and aggressive non-Hodgkin's lymphomas express a homologue of the rat metastasis-associated variant of CD44.

Abstract

SummaryA recently described splice variant of CD44 expressed in metastasizing cell lines of rat tumors, has been shown to confer metastatic potential to nonmetastasizing 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 on human lymphoid cells and tissues and on non-Hodgkin's lymphomas. Normal lymphohematopoietic cells express barely detectable low levels of variant CD44 glycoproteins, whereas 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. It is interesting that overexpression of v6 was also found in several aggressive, but not low-grade, non-Hodgkin's lymphomas.

Loss of Ep-CAM (CO17-1A) expression predicts survival in patients with gastric cancer

“…It was proven that transfection with cDNA encoding one isoform of CD44 converted nonmetastatic carcinoma and sarcoma rat cells into metastatic cells . In human, high CD44 expression was shown to correlate with tumour dissemination and poor prognosis in diffuse large cell lymphoma and in colorectal carcinoma (Koopman et al, 1993;Mulder et al, 1994). CD44 variants containing v6 were also upregulated in activated lymphocytes (Koopman et al, 1993).…”

Alternatively spliced variants of the cell adhesion molecule CD44 and tumour progression in colorectal cancer

“…A range of CD44 alternatively spliced variants, the functions of which are unknown, are expressed in low abundance on some cells of epithelial origin (Terpe et al, 1994), and are also transiently expressed by activated lymphocytes together with CD44s (Koopman et al, 1993). A link between CD44 expression, tumour progression and metastasis has been suggested by studies demonstrating an up-regulation of CD44s and CD44 variants in certain tumours (Jalkanen et al, 1991;Stamenkovic et al, 1989;Wielenga et al, 1993;Hart et al, 1991).…”

Expression of CD44 variant exons in acute myeloid leukemia is more common and more complex than that observed in normal blood, bone marrow or CD34+ cells

“…10 Hematopoietic cells predominantly express CD44H although variant forms containing exons v6, v8, v9 and v10 have been detected in peripheral blood mononuclear cells and in a number of myeloid cell lines 11 and CD44 variants containing v6 and v9 are also transiently expressed during peripheral blood T cell activation. [12][13][14] Altered CD44 variant expression has been demonstrated in a number of malignancies including non-Hodgkin's lymphoma, myeloma and cancers of the breast, gastric mucosa and colon. [15][16][17][18][19][20] Although the nature of the changes in CD44 variant expression have not been consistent in all tumor types the expression of variants containing exon v6 have been associated with tumor dissemination in a number of these tumors.…”