Kisspeptin and GPR54 Receptor Expression in Endometrial Cancer Tissue

Abstract

Kisspeptin (KISS) is a natural peptide—discovered in 1996 as a factor inhibiting the ability to metastasize in malignant melanoma. This protein plays also a regulatory role in the process of puberty, the menstrual cycle, spermatogenesis, implantation and development of the human placenta. The present study aimed to evaluate the expression of KISS and its receptor GPR54 in endometrial cancer (EC) tissue, depending on the histological type of cancer, its stage, various demographic characteristics, and clinical conditions in 214 hysterectomy patients. Expression of KISS and GPR54 was confirmed in 99.5% and 100% of the cases, respectively. Hormone replacement therapy and the coexistence of the anti-Müllerian type 2 receptor in cancer tissue enhanced KISS expression. Smoking, on the other hand, decreased KISS expression. GPR54 expression increased with the advancement of the disease (according to FIGO classification). Also, the presence of the anti-Müllerian type 2 receptor in EC increased the level of GPR54. Hypertension, age and miscarriage harmed the presence of GPR54. The histological type of cancer, diabetes type 2, body mass index, hormonal contraception, number of deliveries, birth weight of newborns, breastfeeding time, and the presence of AMH in EC tissue were not associated with the expression of either KISS nor GPR54. The KISS level was also significantly related to the GPR54 level. Considering that KISS is a non-toxic peptide with antimetastatic properties, further investigation is essential to determine the clinical significance of this peptide.

Kisspeptin Regulates Cell Invasion and Migration in Endometrial Cancer

“…Kisspeptin levels during the periovulatory period are then high and ultimately initiate the LH surge associated with ovulation [ 41 ]. Besides, kisspeptin concentrations are associated with factors such as age, parity, adiposity, insulin sensitivity, and hormonal contraception [ 42 , 43 ]. Current reviews suggest that age impact on Kisspeptin and its receptor expression may be tissue-dependent and should not be correlated with the plasma level of kisspeptin [ 43 ].…”

“…Besides, kisspeptin concentrations are associated with factors such as age, parity, adiposity, insulin sensitivity, and hormonal contraception [ 42 , 43 ]. Current reviews suggest that age impact on Kisspeptin and its receptor expression may be tissue-dependent and should not be correlated with the plasma level of kisspeptin [ 43 ]. It has been shown that Kisspeptin and Kisspeptin receptor can be found in many extrahypothalamic tissues and tumor cells [ 4 , 44 ].…”

“…In human cancers, Kisspeptin and Kisspeptin receptor have been considered endocrine and autocrine regulatory factors regulating cell behavior. In a recent study, expression of Kisspeptin and Kisspeptin receptor was lower in serous, clear cell, and grade 3 endometrioid adenocarcinomas compared with that of low-grade patients [ 43 ]. In addition, loss of immunohistochemical expression of Kisspeptin and Kisspeptin receptor was significantly associated with invasion into deep myometrium and lymphovascular space [ 10 , 43 ].…”

“…In a recent study, expression of Kisspeptin and Kisspeptin receptor was lower in serous, clear cell, and grade 3 endometrioid adenocarcinomas compared with that of low-grade patients [ 43 ]. In addition, loss of immunohistochemical expression of Kisspeptin and Kisspeptin receptor was significantly associated with invasion into deep myometrium and lymphovascular space [ 10 , 43 ]. Metastasis represents the main cause of death for patients with endometrial cancer.…”