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Abstract

Ectopic production of free beta human chorionic gonadotrophin (hCGβ) by bladder carcinoma is well described and occurs in approximately 35% of cases. hCGβ secreting tumours are more aggressive, radioresistant and have a greater propensity to metastasize. We proposed that the ectopic production of hCGβ was contributing in an autocrine fashion to the radioresistance and metastatic potential of such secreting tumours. Though we demonstrated that the addition of hCGβ to the culture media of bladder, cervical and endometrial carcinoma cell lines brought about an increase in cell populations this was not accompanied by a significant increase in the rate of replication. Since a cell population size is a balance of mitosis and mortality, we proposed that hCGβ was inhibiting apoptosis. Here we have demonstrated that following incubation with recombinant hCGβ, bladder carcinoma cells refrain from undergoing apoptosis. Quantitation of apoptotic bodies was carried out by immunoassay and corrected to cell number as determined by MTT assay. In each cell line, addition of hCGβ reduced the number of apoptotic bodies dose-dependently, indicating a diminished apoptotic rate. Furthermore, TGFβ1-induced apoptosis could be dose-dependently inhibited by co-incubation with hCGβ. We propose, therefore, that such a decline in apoptosis may account for the cell population increase previously reported. It may also explain the radioresistance and aggressive nature of hCGβ-secreting tumours and the poor prognosis associated therein. © 2000 Cancer Research Campaign

Free β-human Chorionic Gonadotropin, Total Human Chorionic Gonadotropin and Maternal Risk of Breast Cancer

“…Thus, only the intact α–β complex is hormonally active [12]. Nevertheless, experimental studies have shown that free β-hCG may have both cell growth stimulating [12,13] and inhibitory activities [11], acting via pathways unrelated to its gonadotrophic activities [12].…”

“…Thus, only the intact α–β complex is hormonally active [12]. Nevertheless, experimental studies have shown that free β-hCG may have both cell growth stimulating [12,13] and inhibitory activities [11], acting via pathways unrelated to its gonadotrophic activities [12]. Differences in the biological activity between hCG and free β-hCG has been demonstrated in mammary and other cell types [1,3,11–13].…”

“…In an in vitro study investigating the effects of hCG and its subunits on bladder cancer cell growth, hCG and hCGα had no effect on cell growth, whereas free β-hCG stimulated cell growth [13], which suggests an independent mechanism of action unrelated to its hormone functions. One such mechanism of action is an antiapoptotic effect, which may occur via possible interactions with the TGFβ receptor complex [12]. This is because free β-hCG and TGFβ are structurally similar [12,20], both having an exposed cystine knot making free β-hCG a TGFβ antagonist, while hCG has no exposed cystine knot [21].…”

“…The total hCG assays quantify both intact hCG and free β-hCG, which may have distinct associations with risk of breast cancer. For instance, while total hCG decreases cell proliferation and increases DNA repair in mammary cells [1,3,10], free β-hCG may posses both cellular inhibitory [11] and stimulatory activities in other cells [12,13]. …”

Emerging antibody-based therapeutic strategies for bladder cancer: A systematic review

“…High levels of hCG-β in both the serum and bladder tumors constitute an independent predictor of disease outcome as well as a poor prognostics factor [166]. This protein is thought to be involved in a wide variety of biological events that contribute to tumor growth, including immunosuppressive, anti-apoptotic and angiogenic properties as well as metastasis [168,169]. CDX-1307 actively delivers the hCG-β whole protein to APCs triggering specific and HLA-restricted cellular and humoral responses.…”