A 60 kDa prolactin variant secreted by cervical cancer cells modulates apoptosis and cytokine production

Abstract

Abstract. Prolactin (PRL) is associated with different types of cancer, such as cervical cancer. Recombinant PRL has antiapoptotic effect on cervical cancer cells, and it can also induce cytokine production on macrophages. A 60 kDa variant of PRL is produced by cervical cancer cells. The aim of the present study was to evaluate this variant's bioactivity, to test its effect on cervical cancer cell apoptosis, and to assess its ability to induce cytokine production on THP-1 macrophages. First, 60 kDa PRL was isolated and used to stimulate Nb2 cells. Later, apoptosis was measured after exposure to 60 kDa PRL. Finally, cytokines were measured on THP-1 stimulated supernatants. Our results show that 60 kDa PRL increased Nb2 cell proliferation. Apoptosis was decreased after stimuli with 60 kDa PRL in cervical cancer cells. IL-1β and TNF-α are produced by THP-1 macrophages after stimuli. These results suggest that 60 kDa PRL produced by cervical cancer cells is able to reduce apoptosis in HeLa, SiHa and C-33A cells and induce IL-1β and TNF-α production by THP-1 macrophages.

Identification of a prognostic immune signature for cervical cancer to predict survival and response to immune checkpoint inhibitors

“…A previous study has reported that PRL has antiapoptotic effect on cervical cancer cells. 35 In our study, NRP1 was downregulated in the cervical cancer tissues compared to the normal tissues. However, a recent study has demonstrated that the expression of NRP1 was upregulated in the tumor tissues compared with the cervical intraepithelial neoplasia and normal tissues and high NRP1 expression was correlated with a poorer survival in Chinese patients with CC.…”

Effects of 60�kDa prolactin and estradiol on metabolism and cell survival in cervical cancer: Co‑expression of their hormonal receptors during cancer progression

“…Our previous study discovered the presence of a PRL isoform with a molecular weight of ~60 kDa in the protein extracts and supernatants of HeLa, SiHa and C33A cells, which was absent in HaCaT cells (18). Due to the relevance that has recently been conferred to local PRL in the pathophysiology of some tumors, its bioactivity was initially determined (25). Subsequently, cells were stimulated with this PRL isoform, in order to evaluate the effects of its use separately and in combination with E2 on the mechanisms underlying cell survival and metabolism.…”

“…In UCC, hPRL does not affect proliferation; however, it decreases etoposide-induced cell death; this effect is mediated by the phosphorylation of STAT3 (18,20). Recently, 60 kDa PRL, which was isolated from the supernatant of HeLa cells, was revealed to induce both responses (25).…”

“…Using the Nb2 cell line as a model system to analyze the effects of hPRL on cell mitogenesis, stimulation with 60 kDa PRL was revealed to increase cell growth (23,24). Local 60 kDa PRL has been revealed to exert bioactive effects and to phosphorylate STAT3 (25).…”

The Formation and Therapeutic Update of Tumor-Associated Macrophages in Cervical Cancer

“…A variant of prolactin (PRL) is produced by cervical cancer cells. It reduced apoptosis in HeLa, SiHa and C-33A cell lines and induced IL-1β and TNF-α production by human peripheral blood mononuclear cell line THP-1 macrophages [32]. Higher doses of PRL (1000 ng/mL) induces macrophages to produce anti-inflammatory cytokine IL-10, which leads to a significant decrease in production of proinflammatory cytokines [33].…”