Human Chorionic Gonadotropin-Mediated Induction of Breast Cancer Cell Proliferation and Differentiation

Abstract

Human chorionic gonadotropin (hCG) is a hormone that specifically binds to luteinizing hormone receptor (LHR) and exerts several roles, including the support of pregnancy and fetal gonadal steroidogenesis. Since hCG is also expressed by some tumor types, like breast cancer, many efforts have been made to study its role in neoplesia, with some studies showing a cancer-supportive role and others showing a cancer-protective role. A critical examination of the literature highlighted that the in vitro effect of hCG has been tested in the presence of fetal serum, which contains other gonadotropins, in the culture medium. Thus, we hypothesized that the use of serum in the cell culture medium might influence the cell response to the hCG treatment due to the presence of other hormones. Thus, we analyzed the in vitro effect of highly purified hCG on cell proliferation and the activation of the down-stream signal transduction pathway in three breast cancer cell lines, particularly focusing on MCF7, cultured in serum-deprived conditions. Our data show that hCG increases cell proliferation and activates the down-stream target Akt, together with a decrease of the LHR mRNA expression level. Finally, we also tested the differentiation capacity of hCG on MCF7 cancer stem cells (CSCs) and show that it favors the proliferation and differentiation of these cells, thus suggesting that hCG also renders cells more able to colonize and invade the organs.

A new frontier in therapy personalisation based on in vitro studies to preserve fertility potential of men

“…As reported in Figure 1 b, only Leydig cells respond to hCG treatment by showing increased cell proliferation, whereas Sertoli cells are not affected by the treatment. Another important evaluation that we have confirmed also in this cellular system is that, in order to study the real effect of hCG on cell culture, it is necessary to treat the cells in the absence of foetal bovine serum (FBS), which includes LH and FSH (Dando et al., 2021 ). Among our preliminary series, we found that each cell population responded differently to different dosage schemes, and these differences are visible between different patients' cells, correlating with age (data not yet published).…”

Aberrant trophoblastic differentiation in human cancer: An emerging novel therapeutic target (Review)

“…This hormone reportedly inhibits the proliferation and induces the differentiation of human breast cancer cells in vitro ( 50 ). Paradoxically, a recent study revealed enhanced proliferation and poor differentiation of β-hCG-expressing breast cancer cells, which translated into higher colonization and invasion abilities of these cells ( 51 ). In breast cancer cells, the BRCA1 mutation reportedly promotes β-hCG-mediated tumorigenesis through TGF-βRII signaling ( 52 ).…”

Testicular Torsion: Preliminary Results of In Vitro Cell Stimulation Using Chorionic Gonadotropin

“…RNA extraction and real-time quantitative PCR (qPCR) were performed as previously described [11]. The positive control cells were MCF7 (breast cancer cell line) and the negative control cells were PaCa44 (pancreatic cancer cell line), as previously described [12]. Briefly, total RNA was extracted from 1 × 10 5 cells using a Single Cell RNA Purification Kit (Norgen Biotek, Thorold, ON, Canada) and 0.5 µg of RNA was reversetranscribed using first-strand cDNA synthesis.…”

“…Thus, we quantitatively analyzed the mRNA levels of AR and LHR in gubernacular cells derived from the control patient (i.e., the patient affected by cryptorchidism) and patients #4 and #15. We used a breast cancer cell line (MCF7) for the positive control cells and a pancreatic cancer cell line (PaCa44) for the negative control cells, whose values were undetectable, as previously described [12]. The data reported in Figure 2A show that AR expression was differentially expressed among the two patients.…”

“…As represented in Figure 3A, we treated the cells in vitro with 100 UI/mL hCG for 4 weeks and then analyzed cell proliferation after the end of the 5th w this therapeutic scheme because it was very similar to the posology used certain testicular pathologies. It is noteworthy that, as reported in the Mater ods, cells were treated and maintained in culture in a medium depleted w included LH and FSH [12], in order to evaluate the effect on cell proliferatio only by hCG. As a control, we used gubernacular cells derived from a you years old) who had not been affected by testicular torsion but by crypto reported as the "control patient" (Figure 3B).…”