GnRH analogs reduce invasiveness of human breast cancer cells

Alten, Julia; Fister, Stefanie; Schulz, Hiltrud; Viereck, Volker; Frosch, Karl‐Heinz; Emons, Günter; Gründker, Carsten

doi:10.1007/s10549-006-9222-z

Cited by 38 publications

(54 citation statements)

References 43 publications

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“…In different breast cancer cells lines (HCC70, MCF-7, MDA-MB-435, MDA-MB-453 and T47-D), their invasive capability was increased when these were co-cultured with hOB or MG63 osteosarcoma cells. This effect was reverted after GnRH analog treatments, demonstrating receptor ability to down-regulate cell motility in this cellular model (130) (Fig. 2D).…”

Section: Gnrhr and Ovarian Cancermentioning

confidence: 80%

Human gonadotropin-releasing hormone receptor-activated cellular functions and signaling pathways in extra-pituitary tissues and cancer cells (Review)

Aguilar-Rojas¹

2009

Oncol Rep

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Abstract. Human gonadotropin-releasing hormone receptor (GnRHR) and its natural ligand human gonadotropin-releasing hormone (GnRH) were initially described as signaling complexes that play a key role in reproductive functions. By binding to specific receptors present on pituitary gonadotropes, GnRH regulates the sperm and ovum maturation, as well as steroidogenesis within the context of the hypothalamushypophysis axis. The expression of GnRH and its receptor has clearly been established in many extra-pituitary organs.

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Section: Gnrhr and Ovarian Cancermentioning

confidence: 80%

Human gonadotropin-releasing hormone receptor-activated cellular functions and signaling pathways in extra-pituitary tissues and cancer cells (Review)

Aguilar-Rojas¹

2009

Oncol Rep

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“…Previous work had shown that breast cancer cell invasion through an artificial basement membrane in vitro was increased by coculture with human primary osteoblasts (hOB) or osteoblast-like sarcoma cells [19]. The ability to invade the basement membrane and to migrate in response to the cellular stimulus was significantly reduced after treatment with GnRH-I/-II analogs [19].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, we demonstrated that GnRH-II antagonists bind to the GnRH-I receptor and are clear antagonists at the GnRH-I receptor [17]. Recently, we showed that invasion of breast cancer cells through an artificial basement membrane was increased when they were cocultured with human primary osteoblasts (hOB) [19]. The ability to invade the basement membrane and to migrate in response to the cellular stimulus was significantly reduced after treatment with GnRH analogs [19].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we showed that invasion of breast cancer cells through an artificial basement membrane was increased when they were cocultured with human primary osteoblasts (hOB) [19]. The ability to invade the basement membrane and to migrate in response to the cellular stimulus was significantly reduced after treatment with GnRH analogs [19]. This effect was due to an indirect inhibition of expression of the osteoblast-derived chemokine stromal cell-derived factor-1 (SDF-1).…”

Section: Introductionmentioning

confidence: 99%

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Agonists and antagonists of GnRH-I and -II reduce metastasis formation by triple-negative human breast cancer cells in vivo

Schubert

Hawighorst

Emons

et al. 2011

Breast Cancer Res Treat

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Metastasis to bone is a frequent problem of advanced breast cancer. Particularly breast cancers, which do not express estrogen and progesterone receptors and which have no overexpression/amplification of the HER2-neu gene, so called triple-negative breast cancers, are considered as very aggressive and possess a bad prognosis. About 60% of all human breast cancers and about 74% of triple-negative breast cancers express receptors for gonadotropin-releasing hormone (GnRH), which might be used as a therapeutic target. Recently, we could show that bone-directed invasion of human breast cancer cells in vitro is time- and dose-dependently reduced by GnRH analogs. In the present study, we have analyzed whether GnRH analogs are able to reduce metastases of triple-negative breast cancers in vivo. In addition, we have evaluated the effects of GnRH analogs on tumor growth. To quantify formation of metastasis by triple-negative MDA-MB-435 and MDA-MB-231 human breast cancers, we used a real-time PCR method based on detection of human-specific alu sequences measuring accurately the amount of human tumor DNA in athymic mouse organs. To analyze tumor growth, the volumes of breast cancer xenotransplants into nude mice were measured. We could demonstrate that GnRH analogs significantly reduced metastasis formation by triple-negative breast cancer in vivo. In addition, we could show that GnRH analogs significantly inhibited the growth of breast cancer into nude mice. Side effects were not detectable. In conclusion, GnRH analogs seem to be suitable drugs for an efficacious therapy for triple-negative, GnRH receptor-positive human breast cancers to prevent metastasis formation.

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“…The GnRH system has been reported to play an autocrine/paracrine role in the inhibition of cellular growth and metastatic potential in breast cancer cell lines [24,35], and breast tumor regression in nude mouse [14,26]. However, its expression was associated with a protective effect on the chemotherapeutic drug-produced apoptosis [30].…”

Section: Introductionmentioning

confidence: 99%

Gonadotropin-releasing hormone neuropeptides and receptor in human breast cancer: Correlation to poor prognosis parameters

et al. 2013

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a b s t r a c tExpression of the two gonadotropin-releasing hormone homologue peptides GnRHI and GnRHII and their receptor GnRHR has been demonstrated in a number of malignancies. In hormone-dependent breast cancer, GnRH analogs are used for therapy in premenopausal women. Gene expression of GnRHI, II and R was studied in breast biopsies from primary breast adenocarcinoma obtained from the tumor and the adjacent benign tissue. Levels were evaluated by a multiplex real-time RT-PCR. GnRHI transcripts were detected in 14.7% of the benign and 29.4% malignant biopsies and GnRHII in 21.2% benign and 44.1% malignant biopsies. GnRHR was also more frequent in the malignant (54.2%) than in the benign (24.0%) biopsies, at similar expression levels. No transcripts were detected in biopsies from healthy individuals. There was a strong correlation between the presence of GnRHI and GnRHII transcripts and their receptor in the benign and the malignant biopsies. GnRHI, II and R expression correlated significantly with poor prognosis pathological parameters. Immunohistochemistry for GnRHR revealed expression in malignant cells and in epithelial cells of mammary ducts of the adjacent area with pre-cancerous features. In contrast, GnRH I and II peptides were rarely expressed at low levels in breast cancer cells. In conclusion GnRH peptides and receptor are expressed more frequently in breast tumors than in the adjacent mammary tissue, representing a malignant feature. Their expression correlated to tumor characteristics of poor prognosis and was therefore related to more aggressive malignancies. Concomitant expression of peptides and receptor supports an autocrine/paracrine regulating role.

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GnRH analogs reduce invasiveness of human breast cancer cells

Cited by 38 publications

References 43 publications

Human gonadotropin-releasing hormone receptor-activated cellular functions and signaling pathways in extra-pituitary tissues and cancer cells (Review)

Human gonadotropin-releasing hormone receptor-activated cellular functions and signaling pathways in extra-pituitary tissues and cancer cells (Review)

Agonists and antagonists of GnRH-I and -II reduce metastasis formation by triple-negative human breast cancer cells in vivo

Gonadotropin-releasing hormone neuropeptides and receptor in human breast cancer: Correlation to poor prognosis parameters

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