UroToday.com Prostate cancer has posed a major public health problem in the United States and worldwide. There is a continuous search for better diagnostic markers and therapeutic targets for this disease. Galectin3 is a βgalactosidebinding protein, which binds to the carbohydrate portion of cell surface glycoproteins or glycolipids (1, 2). It has been implicated in a variety of biological functions including cell proliferation, apoptosis, angiogenesis, tumor progression and metastasis.

A growing body of literature describes the correlation of galectin3 with neoplastic progression. In human prostate cancer, galectin3 expression was reported to be downregulated with progressive stages (36), while in many other cancers like thyroid, gastric carcinoma, and squamous cell carcinoma of the head and neck, galectin3 expression was upregulated with increased malignant phenotype (79). Recently, in vivo cleavage of galectin3 was reported in breast cancer using two specific antibodies a monoclonal antibody, which recognizes intact galectin3 and a polyclonal antibody, which recognizes both intact and cleaved galectin3 (10) . We questioned whether cleavage of galectin3 might be also a part of prostate cancer progression and could be detected in biopsies. In our study, we evaluated the role of galectin3 during the progression of human prostate cancer using two approaches

1) staining human prostate cancer tissues with differential antibodies,

2) investigating the association of galectin3 with biological behavior of prostate cancer PC3 cells by silencing its expression.

Human prostate cancer tissue array was analyzed by immunohistochemistry using two differential antigalectin3 antibodies. We found that no cleavage of galectin3 occurred in normal or PIN tissue samples, however, in Gleason 3 and 4 cancer tissues, a significantly higher percentage of positive samples and more galectin3 positive cells in the same section using polyclonal antibody compared to the monoclonal antibody indicate the cleavage of galectin3. Our data demonstrated that galectin3 is cleaved during the malignant transformation of human prostate cancer, which suggested that cleavage of galectin3, not just the presence of intact galectin3, could be used as the maker for diagnosis of prostate cancer. To date, the actual biological functions of galectin3 in prostate cancer have not been well described. Our study showed that silencing of galectin3 using siRNA in PC3 cells contributed to reduced cell migration and cell invasion, which may be conducted by suppression of MMP2/MMP9 activities. Significant evidence has shown that galectin3 is implicated in modulation of tumor cells growth. In our study, galectin3 knockdown reduced cell growth of prostate cancer PC3 cells and induced cell cycle arrest at G1 phase. The G1 cell cycle arrest seemed to be due to upregulation of p21 expression and its nuclear localization, moreover, downstream pRb displayed hypophosphorylation which inhibits the transcription of genes required to traverse G1 to S phase. A relationship of galectin3 expression with tumorigenic phenotype of many cancer cells has been demonstrated. We showed here that PC3 cells with silencing of galectin3 displayed reduced colony size and efficiency of colony formation in soft agar. Loss of galectin3 expression also resulted in reduced tumor growth when cells were injected in the ventral prostate of nude mice. Taken together with observations in other tumor types, it could be postulated that galectin3 expression is associated with maintenance of tumorigenic potential of cancer cells.

In conclusion, our data show that galectin3 is cleaved during the progression of prostate cancer and might be associated with metastasis, cell growth, and tumorigenicity of PC3 cells. Expression of intact versus cleaved galectin3 thus might be used as a marker for prognosis of prostate cancer and a therapeutic target for the treatment of prostate cancer.

References
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5. Ahmed H, Banerjee PP, Vasta GR. Biochem Biophys Res Commun, 3582416, 2007.
6. Merseburger AS, Kramer MW, Hennenlotter J, Simon P, et al. Prostate, 68727, 2008.
7. Saggiorato E, Aversa S, Deandreis D, Arecco F, et al. J Endocrinol Invest, 273117, 2004.
8. Miyazaki J, Hokari R, Kato S, Tsuzuki Y, et al. Oncol Rep, 9130712, 2002.9. Gillenwater A, Xu XC, elNaggar AK, Clayman GL, Lotan R. Head Neck, 1842232, 1996.
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Written by Avraham Raz, MD et al. as part of Beyond the Abstract on UroToday.com

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