Sperm-Associated Antigen 9 Is Associated With Tumor Growth, Migration, and Invasion in Renal Cell Carcinoma

Abstract

Renal cell carcinoma (RCC) represents one of the most resistant tumors to radiation and chemotherapy. Current therapies for RCC patients are inefficient due to the lack of diagnostic and therapeutic markers. Our recent studies have suggested an association of sperm-associated antigen 9 (SPAG9) with ovarian carcinomas. In the present study, we investigated the clinical relevance of SPAG9 in RCC patients. RT-PCR analysis showed expression of SPAG9 transcript in RCC tissues and RCC cell lines. In situ RNA hybridization and immunohistochemistry analyses confirmed the expression of SPAG9 in 88% of cancer patients, suggesting that SPAG9 participates in renal cancer. In addition, immunoblotting and ELISA analyses revealed a humoral immune response against SPAG9 in the sera of RCC patients but not in healthy individuals. Consistent with the clinical findings, knockdown of SPAG9 expression in RCC cells with specific siRNA significantly reduced cell growth and colony formation. Using in vitro wound healing and Matrigel invasion assays, we found that cell migration and invasive ability were also significantly inhibited. Furthermore, in vivo xenograft studies in nude mice revealed that administration of a SPAG9 siRNA plasmid significantly inhibited tumor growth. In conclusion, SPAG9 expression is associated with clinicopathologic features of tumors, suggesting that SPAG9 could contribute to the early spread of cancer. These results indicate that SPAG9 may have a role in tumor development and metastasis and thus could serve as a novel target for early detection and treatment of RCC. [Cancer Res 2008;68(20):8240-8]

Sperm-Associated Antigen 9 is a Promising marker for Early Diagnosis of Endometrial Cancer

“…SPAG9 gene is located at the chromosome 17q21, which is a region involved in amplification and expression of cancer-related genes (Jagadish et al, 2005b). Although it was originally thought to be expressed exclusively in testis, ongoing research revealed SPAG9 expression in numerous tumors originating from various sites and organs such as brain, thyroid, breast, lung, kidney, colon, ovary, cervix, and endometrium (Garg et al, 2008, Garg et al, 2009a, Garg et al, 2009b, Kanojia et al, 2009, Kanojia et al, 2011, Yu et al, 2012, Wang et al, 2013, Yi et al, 2013. In a study by Garg et al (2007), SPAG9 expression and host immune responses were investigated in epithelial ovarian cancer (EOC) specimens and human ovarian cancer cell lines (Garg et al, 2007).…”

Sperm‐associated antigen 9 is a biomarker for early cervical carcinoma

“…16 The JNK signaling interaction is well known to play an important regulatory role in cell proliferation, differentiation, apoptosis, cellular transformation, and tumor cell growth, and may be equally important for the outcome of SPAG9 expression in the cervix. 16,27,28 To our knowledge, the mechanism underlying the association between SPAG9 and carcinogenesis is still unclear. Perhaps the overexpression of SPAG9 changes the stability or kinetics of MAPK signaling pathways, leading to facilitation of cell invasion and migration; this warrants further studies.…”

Sperm-Associated Antigen 9 Is a Novel Biomarker for Colorectal Cancer and Is Involved in Tumor Growth and Tumorigenicity

“…COLO 205 or HCT 116 cells (1 ϫ 10 5 ) were plated in 6-well plates, allowed to attach, and were transiently transfected using Lipofectamine reagent (Invitrogen, Life Technologies, Carlsbad, CA) according to the manufacturer's instructions and as described previously. 13 …”

“…6,12 Cancer-specific alternatively spliced mRNAs and protein isoforms may be used as cancer biomarkers. Our recent study demonstrated SPAG9 expression and its association with clinicopathological characteristics of tumors in renal cell carcinoma, 13 epithelial ovarian cancer, 14 breast cancer, 15 cervical carcinoma, 16 and thyroid cancer. 17 These findings suggest that SPAG9 may have a role in early spread of disease.…”