The Roles of Glycodelin in Cancer Development and Progression

Abstract

Glycodelin is a kind of glycoprotein expressed in secretory endometrium, pregnancy deciduas, and amniotic fluid originally, which is vital for the maintenance of normal human reproductive activities. Recent researches have reported that glycodelin is specifically expressed in various malignancies, including female-specific cancers such as endometrial cancer, ovarian cancer and breast cancer, and non-gender specific cancers including lung cancer, and colon cancer, and glycodelin expression correlates with the diagnosis and prognosis of cancer patients. This review focuses on the expression of glycodelin in different cancers and its role in cancer development and progression. Glycodelin possesses the abilities to regulate cancer cell proliferation, differentiation, and invasion, promote cancer angiogenesis, and modulate the differentiation and function of immune cells including T cells, dendritic cells, monocyte-macrophages, natural killer cells and B cells participating in cancer development. The expression of glycodelin can be regulated by stromal cells, lysophosphatidic acid, histone deacetylase inhibitors, and relaxin. In summary, glycodelin is a promising biomarker for the diagnosis and prognosis of cancer patients, and depending on its distinct immunoregulatory effects, glycodelin can be a prospective target for cancer immunotherapy.

Insights into the hyperglycosylation of human chorionic gonadotropin revealed by glycomics analysis

“…The Hu-FEDS hypothesis also predicts that tumour cells employ the same carbohydrate functional groups used in the pregnant uterus to evade the human immune response [52]. Consistent with this concept, hCG and other pregnancy-related glycoproteins are often upregulated in tumour cells [54][55][56][57].…”

Clinical and Histopathological Parameters Correlate with Microvessel Density but Not with Vascular Endothelial Growth Factor Expression in Ovarian Cancer

“…Considering these aspects, vascular endothelial cadherin (VEC) has gained interest in the research field of ovarian cancers due to its role in activating endothelial genes and triggering stability-related genes thus exerting a direct influence on the ovarian carcinoma vasculature [30]. Also, glycodelin is an important promoter of tumor angiogenesis in ovarian cancer and influences the differentiation and function of immune cells such as T and B cells, dendritic cells, macrophages and NK cells [31]. Under these circumstances, glycodelin may become an effective target in antiangiogenic therapy and immunotherapy in ovarian cancers.…”

The Role of Glycodelin in the Regulation of the Immune System in the Context of Developing Pregnancy

“…Finally, it is worth noting that GdA expression is observed not only in healthy tissues of the reproductive tract, but also in certain types of cancer: lung, breast, endometrium, ovaries, and melanoma cells [28,57,64,65,82]. It has been shown that GdA can be used as a biomarker to track the progression of a tumor, as has been shown in non-small cell lung cancer, recurrence or metastatic spread [11]. Understanding the regulation of the glycodelin expression may lead to the development of new therapeutic approaches, with the help of which it will be possible to weaken the system of protection of the tumors themselves.…”

“…Neither glycosylation nor sialylation of glycodelin does not impair the ability of monocytes to chemotaxis. Recombinant GdA binds to a specific protein receptor in monocytes, but the corresponding receptor is not detected on the surface of T or B cells [11]. Further study of the GdA action mechanism established that on the surface of cells of the monocyte-macrophage lineage, the binding protein for glycodelin is the L-selectin molecule.…”