Sperm protein 17 is expressed on normal and malignant lymphocytes and promotes heparan sulfate–mediated cell-cell adhesion

Abstract

Sperm protein 17 (Sp17) is a highly conserved mammalian protein present on acrosome-reacted sperm that is thought to promote fertilization by binding sulfated carbohydrates of the oocyte zona pellucida. Although Sp17 was originally described as a testis-specific antigen, emerging evidence indicates that it may be more ubiquitously expressed than was previously thought. With the use of a specific antiserum, Sp17 was found to be present on the surface of malignant lymphoid cells, including B- and T-lymphoid cell lines, and on the surface of primary cells isolated from 2 patients having B-lymphoid tumors. Surprisingly, circulating B lymphocytes isolated from healthy volunteers also expressed Sp17, while circulating T lymphocytes exhibited only very weak expression. The role of Sp17 in promoting lymphoid cell adhesion was addressed with the use of recombinant Sp17 (rSp17). The rSp17 binds to the surface of myeloma cells but not to cells pretreated with heparitinase, an enzyme that removes heparan sulfate from the cell surface. Moreover, rSp17 promotes extensive aggregation of cells that express the syndecan-1 heparan sulfate proteoglycan, but in contrast, cells lacking syndecan-1 expression fail to aggregate in the presence of rSp17. These findings suggest that Sp17 promotes heparan sulfate-mediated cell aggregation and thereby plays a role in regulating adhesion and migration of normal and malignant lymphocytes.

Increased levels of sperm protein 17 mRNA and circulating antibodies in periampullary carcinoma patients

“…However, a research group reported the expression of Sp17 on ciliated cells [7]. In addition to this, Wen et al and Lacy et al found a carbohydrate-binding region in the central portion of the Sp17 peptide, which is thought to be implicated in cell-cell adhesion [8,9]. All of these facts, including the expression of Sp17 mRNA in metastatic cells but not in transitional phases [10], are suggestive of the significance of Sp17 in cancer metastasis, such as in the proliferation, migration, and/or signaling of tumor cells.…”

Sperm protein 17 (Sp17) is a suitable target for immunotherapy of multiple myeloma

“…A recent paper suggested that Sp17 might be expressed in normal leukocytes, casting doubt on the safety of Sp17 as a tumor vaccine. 21 Based on the results presented in this manuscript showing the lack of killing of autologous monocyte-derived DCs and EBV-transformed LCLs, and our recent work using immunocytochemistry and immunohistochemistry failing to demonstrate that Sp17 protein is expressed by normal leukocytes, 14 a phase I/II pilot study has been initiated in our institution for the use of Sp17-pulsed DCs for patients with residual disease following treatment for MM. It, however, remains to be determined whether the laboratory results reported here can be translated into clinical successes in our pilot study.…”

Cancer immunotherapy targeting Sp17: When should the laboratory findings be translated to the clinics?

“…Sp17 plays a key role in the interaction of sperm with the zona pellucida during fertilization [21,22]. Sp17 also promotes heparan sulfate-mediated cell-cell adhesion [23,24], suggesting a potential role for Sp17 in normal physiology.…”