Cancer/testis (CT) antigens, carcinogenesis and spermatogenesis

Abstract

During spermatogenesis, spermatogonial stem cells, undifferentiated and differentiated spermatogonia, spermatocytes, spermatids and spermatozoa all express specific antigens, yet the functions of many of these antigens remain unexplored. Studies in the past three decades have shown that many of these transiently expressed genes in developing germ cells are proto-oncogenes and oncogenes, which are expressed only in the testis and various types of cancers in humans and rodents. As such, these antigens are designated cancer/testis antigens (CT antigens). Since the early 1980s, about 70 families of CT antigens have been identified with over 140 members are known to date. Due to their restricted expression in the testis and in various tumors in humans, they have been used as the target of immunotherapy. Multiple clinical trials at different phases are now being conducted with some promising results. Interestingly, in a significant number of cancer patients, antibodies against some of these CT antigens were detected in their sera. However, antibodies against these CT antigens in humans under normal physiological conditions have yet to be reported even though many of these antigens are residing outside of the blood-testis barrier (BTB), such as in the basal compartment of the seminiferous epithelium and in the stem cell niche in the testis. In this review, we summarize latest findings in the field regarding several selected CT antigens which may be intimately related to spermatogenesis due to their unusual restricted expression during different discrete events of spermatogenesis, such as cell cycle progression, meiosis and spermiogenesis. This information should be helpful to investigators in the field to study the roles of these oncogenes in spermatogenesis.

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

“…This property of CT antigens make them attractive target for cancer immunotherapy. To date, about 70 families of CT antigens have been identified, comprising about 140 members [4]. Sperm protein 17 (Sp17) is a CT antigen whose gene is localized to chromosome 11 in humans.…”

rpS6 Regulates Blood-Testis Barrier Dynamics By Affecting F-Actin Organization and Protein Recruitment

“…spermiogenesis) behind the host immune system, so that these cellular events all take place in a specialized microenvironment, namely the adluminal compartment (1,2). This is to avoid the production of antisperm antibodies against germ-cell-specific antigens that are expressed transiently in developing spermatids, many of which are proto-and/or oncogenes (3). The BTB is also one of the tightest blood-tissue barriers in the mammalian body (1).…”

Emerging roles for PIWI proteins in cancer

“…The molecular details underlying the oncogenic activities of PIWI remain to be fully addressed, but PIWIs have been found to regulate the occurrence of those cancer hallmarks [27,28]. Because PIWI proteins are predominantly expressed in germ cells and are ectopically expressed in tumors, they are candidate cancer/testis antigens (CTAs) [29,30]. CTAs are expressed predominantly in the testis and in various types of cancers.…”