Abstract
Loss of immunosurveillance is a major cause of cancer progression. Here, we demonstrate that gelsolin, a constituent of ejaculate, induces apoptosis of activated lymphocytes in prostate cancer. Gelsolin was highly expressed in prostate cancer cells, and was associated with tumor progression, recurrence, metastasis, and poor prognosis. In vitro, secreted gelsolin inactivated CD4+ T cells by binding to CD37, and induced apoptosis of activated CD8+ T lymphocytes by binding to Fas ligand during cell contact dependent on major histocompatibility complex I. Moreover, secreted gelsolin bound to sortilin, which in turn bound to Wiskott-Aldrich syndrome protein family member 3, thereby enhancing the endocytosis and intracellular transport of essential lipids needed to facilitate tumor growth and expansion. Under normal conditions, gelsolin is a seemingly harmless protein that prevents immune responses in female recipients. In disease states, however, this protein can inhibit immunosurveillance and promote cancer progression.
Highlights
Prostate cancer (PCa) is the second-leading cause of cancer-related death in the USA male patients, which accounts for about 10% of cancer-related deaths [1]
Statistical results showed that gelsolin expression in PCa was associated with disease status, tumor grade, cigarette smoking, serum prostate-specific antigen (PSA) level, lymphovascular infiltration and the expression of androgen receptor, aldo-keto reductase 1C2 (AKR1C2) and epidermal growth factor receptor (EGFR) (Table 1)
Pathology studies further demonstrated that the overexpression of gelsolin in patients with PCa was associated with significantly higher incidence of early tumor recurrence and metastasis, as well as reduced patient survival
Summary
Prostate cancer (PCa) is the second-leading cause of cancer-related death in the USA male patients, which accounts for about 10% of cancer-related deaths [1]. In Scandinavian and Baltic countries, the incidence rate of PCa is equivalent to that in central Europe and USA, the mortality rate is much higher, average around 34.5/105 men [1]. In patients with more www.impactjournals.com/oncotarget advanced diseases, those with bone metastasis (~70% of advanced PCa patients) [2, 3], even androgensensitive tumor cells become resistant to radiation and conventional chemotherapeutic agents (e.g., Adriamycin, cisplatin, etoposide, 5-fluorouracil, methotrexate, mitoxantrone, vincristine and vinblastine) [4]. The mechanisms underlying such spontaneous resistance to radiation and anticancer drugs, as well as the propensity for bone metastasis, are not well understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
