Ghrelin is a prognostic marker and a potential therapeutic target in breast cancer

Abstract

Ghrelin and obestatin are gastrointestinal peptides, encoded by the same preproghrelin gene. Both are expressed in breast cancer tissue and ghrelin has been implicated in breast cancer tumorigenesis. Despite recent advances in breast cancer management the need for new prognostic markers and potential therapeutic targets in breast cancer remains high. We studied the prognostic impact of ghrelin and obestatin in women with node negative breast cancer.Within a cohort of women with breast cancer with tumor size ≤ 50 mm, no lymph node metastases and no initiation of adjuvant chemotherapy, 190 women were identified who died from breast cancer and randomly selected 190 women alive at the corresponding time as controls. Tumor tissues were immunostained with antibodies versus the peptides.Ghrelin expression was associated with better breast cancer specific survival in univariate analyses (OR 0.55, 95% CI 0.36–0.84) and in multivariate models, adjusted for endocrine treatment and age (OR 0.57, 95% CI 0.36–0.89). Obestatin expression was non-informative (OR 1.2, 95% CI 0.60–2.46). Ghrelin expression is independent prognostic factor for breast cancer death in node negative patients—halving the risk for dying of breast cancer. Our data implies that ghrelin could be a potential therapeutic target in breast cancer treatment.

No effect of administration of unacylated ghrelin on subcutaneous PC3 xenograft growth in a Rag1−/− mouse model of metabolic dysfunction

“…It has recently been recognised that UAG can under some conditions act as a functional ghrelin inhibitor, reducing ghrelin-mediated increases in plasma glucose [22, 26, 28, 72] and lipid [27, 29]. As the ghrelin axis also plays a role in the progression of a number of endocrine-related cancers [5, 32–34], including prostate cancer [5, 43], we hypothesised that UAG may have beneficial effects in advanced prostate cancer associated with metabolic syndrome. To evaluate this hypothesis, we examined the effect of UAG on a prostate cancer cell line in vivo .…”

“…This includes prostate cancer, a classical endocrine-related cancer and the most commonly diagnosed cancer in American men after skin cancer [36], where acylghrelin increases cell proliferation and migration [5, 14, 37–46]. UAG also has functional effects in several cancers, including prostate cancer [5, 32–34, 43]. In the PC3 prostate cancer cell line, UAG has a biphasic effect, reducing cell proliferation at supraphysiological levels (10nM-1μM) [14].…”

The role of Ghrelin Receptor Expression in the Diagnosis of breast cancer

“…Complete and/or partial staining with any intensity (>50% IR tumor cells) was designated as positive staining that differs from truly negative staining (< 50% IR tumor cells), background and diffuse non-speci ic staining. The staining of cytoplasmic that can be observed with highpower ields (40X objective) was considered a positive reaction (Grönberg et al, 2017).…”

“…It was reported that Ghrelin had a wide variety of physiological functions that range from regulation of food intake, hormonal secretion, insulin secretion modulation, adipogenesis and gastrointestinal motility, and one of the most important orexigenic peptides currently known. The possible role of Ghrelin in tumorigenesis might be contributed to its involvement in proliferation of cells and the stimulation of milk production, together with the its stimulatory effect on Growth hormone levels via Ghrelin axis, in addition to its high levels in females (Chopin et al, 2011;Delporte, 2013;Khatib et al, 2014;Grönberg et al, 2017).…”

“…Several types of research conducted previously on the Ghrelin system and its role in the regulation of the processes of the progression and development of breast carcinoma still not fully comprehensive and could not provide a solution to the emerging con licts. It was reported clearly that Ghrelin participates in the inhibition of breast carcinoma proliferation in humans that may be used in the future as a promising treatment for breast cancer (Grönberg et al, 2017). It was obviously demonstrated that Ghrelin's expression associates signi icantly with the positivity of estrogen receptor, low histologic grade, low rate of proliferation and small tumor size in human breast tumors.…”