Elevated expression of secreted autocrine growth factor progranulin increases cervical cancer growth.

Abstract

Little is known about the role of progranulin (PGRN) in cervical cancer, which is an autocrine growth factor. We used immunohistochemistry, western blot, and ELISA to determine the expression levels of PGRN in cervical cancer and cervical cancer cell lines. Immortalized normal cervical cell line H8 with lower PGRN expression was treated with recombinant human PGRN (rhPGRN) and forced expression of PGRN by transfection and cell proliferation were determined. PGRN knockdown by siRNA was also performed in HeLa cells with high PGRN expression and cell proliferation was also determined. Furthermore, H8 cell xenograft mouse model was employed to determine if PGRN treatment could increase tumorigenesis of H8 cell xenograft. Our results showed that PGRN expression was significantly increased in cervical cancer tissue and high expression of PGRN is closely correlated with the degree of malignancy in cervical cancer cell lines. Increased PGRN expression or rhPGRN treatment increased the proliferation of H8 cells. Consistently, PGRN knockdown in HeLa cells by siRNA transfection reduced proliferation of HeLa cells. In H8 cell xenograft model, both intraperitoneal and intratumoral rhPGRN treatments increased tumorigenic capacity of H8 cell line. Our results suggested that PGRN could be used as both a diagnostic biomarker and therapeutic target.