Immunohistochemical Expression of SFRP1 and SFRP3 Proteins in Normal and Malignant Reproductive Tissues of Rats and Humans

Abstract

Secreted frizzled-related proteins 1 and 3 (SFRP1 and SFRP3) act as Wnt signaling pathway antagonists and play an important role in embryonic development and carcinogenesis. The aim of the present study was to analyze immunohistochemically the distribution of 2 SFRP family proteins, SFRP1 and SFRP3, in an experimental rat model, in normal and intrauterine growth-restricted (IUGR) human placentas, and in a subset of the corresponding human trophoblastic tumors (pure choriocarcinomas and mixed germ cell tumors with choriocarcinoma component). In rats, expression of both SFRP1 and SFRP3 was pronounced in the perimetrium and myometrium, whereas decidual cells showed only occasional positive cytoplasmic staining. The most prominent expression of both proteins was found in blood vessel endothelial cells. Stereological variable of volume density (Vv, mm) showed statistically higher expression of SFRP1 and SFRP3 in human IUGR placentas than in normal pregnancy placentas (P<0.0001). Compared with adjacent normal/benign tissues, reduced expression of SFRP1 and SFRP3 was observed in human trophoblastic tumors (58.5% and 31.25%, respectively), although none of the examined tumors exhibited complete loss of either protein. Our study indicates that increased expression of both SFRP1 and SFRP3 may contribute to the pathogenesis of IUGR placental dysfunction, whereas the loss of these proteins may be involved in the development of human trophoblastic tumors.

The expression of SFRP1, SFRP3, DVL1, and DVL2 proteins in testicular germ cell tumors

“…SFRP proteins antagonize the canonical Wnt signaling through binding to its components, thereby inhibiting their downstream signaling activities . We previously reported that germ cell tumors with trophoblastic differentiation (choriocarcinomas) frequently exhibit loss of SFRP1 and SFRP3 proteins . In the present study, we tested a cohort of germ cell tumors of the testis and found a substantial loss (median expression in tumor cells ~5–10%) of both proteins in comparison with adjacent atrophic/benign testicular tissue.…”

“…Wnt signaling pathway plays an important role in the differentiation of the testis as well as spermatogenesis. The status of SFRP and DVL proteins is largely unknown in testicular germ cell tumors, with only a few published studies that show loss of SFRP1 protein expression in testicular tumors , whereas expression of DVL1 and DVL2 has not been examined, to our knowledge. In this study, we aim to investigate the expression of SFRP1, SFRP3, DVL1, and DVL2 proteins in germ cell tumors of the testis.…”

Cardiac Remodeling: Endothelial Cells Have More to Say Than Just NO

“…Frizzled-related protein 3 (FRP-3) is a member of the Wnt signaling pathway and plays important roles during cardiac embryogenesis. Expression of FRP-3 in ECs has also been confirmed by immunohistological staining in reproductive tissues (Partl et al, 2014 ). Currently, there are no known effects of FRP-3 on cardiac contractility, but it has been shown that FRP-3 expression is increased in failing human myocardium, with a decline following LV assist device therapy (Askevold et al, 2014 ), indicating that FRP-3 is related to heart failure progression, and its secretion dependent on ventricular wall strain.…”

Expression Levels and Localizations of DVL3 and sFRP3 in Glioblastoma

“…In placenta, sFRP3 expression was confined to blood vessel endothelial cells, while decidual cells showed only occasional weak cytoplasmic staining. Perimetrium and myometrium were also positive for sFRP3 expression [ 37 ]. We demonstrated that DVL3 and sFRP3 proteins were present in glioblastoma tissue samples.…”