Differential expression of genes by tumor cells of a low or a high malignancy phenotype: The case of murine and human Ly-6 proteins

Abstract

Progression of tumor cells toward a high malignancy phenotype and metastasis is a multi‐event cascade involving inter alia alterations in the expression of various genes. The focus of our laboratory is on genes whose altered expression may lead, directly or indirectly, to an increased malignancy phenotype. The identification of such genes and the evaluation of the consequences of their altered expression is essential for attempts to halt tumor progression and prevent metastasis formation. Published work originating in our laboratory showed that members of the murine Ly‐6 supergene family are involved in the progression of certain mouse tumors. The expression level of several members of this family was higher on highly malignant cells than on tumor cells expressing a lower malignancy phenotype. Sorting by flow cytometry of tumor cells to subpopulations expressing either high or low levels of Ly‐6E.1 yielded correspondingly cells expressing a high or a low malignancy phenotype. The high malignancy, high Ly‐6E.1‐expressing cells also expressed high levels of the receptor for urokinase plasminogen activator (uPAR), whereas low malignancy, low Ly‐6E.1‐expressing cells also expressed low levels of uPAR. Transfection studies indicated that uPAR was causally involved in conferring a high malignancy phenotype upon tumor cells expressing high levels of Ly‐6E.1. E48 is a human homologue of the murine ThB protein, a member of the Ly‐6 supergene family (but distinct from the Ly‐6E.1 protein mentioned above) and expressed on head and neck squamous carcinoma cells. Experiments currently in progress are aimed to find out whether E48 is involved in the progression of such cancer cells. Using the differential display technology, it was shown that ligation of E48 on tumor cells by the corresponding antibodies (serving as a surrogate for an as yet unidentified E48 ligand) upregulates an enzyme (FX) involved in the biosynthesis of GDP‐L‐fucose. Fucose is an essential component of certain selectin ligands. J. Cell. Biochem. Suppl. 34:61–66, 2000. © 2000 Wiley‐Liss, Inc.

Two genetic variants in prostate stem cell antigen and gastric cancer susceptibility in a chinese population

“…PSCA is located on chromosome 8q24.2 and encodes a cell surface glycoprotein PSCA, which belongs to the Ly‐6/Thy‐1 family of glycosylphosphatidylinositol anchored surface protein 18. Although the definitive function of PSCA has not been clarified either in normal cellular processes or tumorigenesis, proteins in the Ly‐6 family have been reported to be associated with tumorigenesis and tumor cell adhesion 19, 20. The Thy‐1 family has versatile functions in cell adhesion, proliferation, survival, and cytokine/growth factor responses 21.…”

Immunotherapy for Prostate Cancer: Lessons from Responses to Tumor-Associated Antigens

“…It is shown that PSCA, like other GPI-anchored proteins, is involved in the survival of stem cells, in T-cell activation and proliferation, and in cytokine and growth factor responses (97, 98). Furthermore, several studies have connected the Ly-6 family of PSCA-like GPI-anchored proteins to tumor growth and metastazation (99–102). …”

Prostate stem cell antigen: A prospective therapeutic and diagnostic target

“…Additionally, proteins in the Thy-1 family have been reported to function in T cell activation and proliferation, stem cell survival, and cytokine and growth factor responses [10]. Furthermore, the family of Ly-6 genes has been associated with carcinogenesis [11, 12], cellular activation [13] and cell adhesion of tumor cells [14]. While these studies point to potential roles of PSCA, no definitive function has been attributed to the protein either in normal cellular processes or abnormal tumorigenesis.…”