hCGβ expression by cervical squamous carcinoma –<i>in vivo</i> histological association with tumour invasion and apoptosis

Dong, Lei; Wen, Xuesong; Ghali, Lucy; Al-Shalabi, F. M.; Docherty, Suzanne M.; Purkis, Patricia E.; Iles, Ray K.

doi:10.1111/j.1365-2559.2008.03082.x

Cited by 49 publications

(22 citation statements)

References 26 publications

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“…This data is considered rather controversial. New data, however, seemingly confirms these findings in cervical cancer cells [99]. Other studies indicate a clear association between detection of free β-subunit in serum samples, or detection of its degradation product, β-subunit core fragment, in urine samples, with cases with poor grade and advanced stage cancer, or poor outcome malignancy [100-103].…”

Section: Biological Function Of Free β-Subunitmentioning

confidence: 79%

“…These studies together indicate that expression of free β-subunit leads to a negative outcome in human malignancies. Multiple reports now indicate that free β-subunit may have a specific role in malignant transformation of cells [97,99,105-109]. In these, and other studies, stimulation of malignant cell growth has been demonstrated by the action of free β-subunit [97,99,105-109].…”

Section: Biological Function Of Free β-Subunitmentioning

confidence: 96%

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Biological functions of hCG and hCG-related molecules

Cole

2010

Reprod Biol Endocrinol

379

296

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BackgroundhCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions. These are hCG produced by villous syncytiotrophoblast cells, hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non-trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary.Results and discussionhCG has numerous functions. hCG promotes progesterone production by corpus luteal cells; promotes angiogenesis in uterine vasculature; promoted the fusion of cytotrophoblast cell and differentiation to make syncytiotrophoblast cells; causes the blockage of any immune or macrophage action by mother on foreign invading placental cells; causes uterine growth parallel to fetal growth; suppresses any myometrial contractions during the course of pregnancy; causes growth and differentiation of the umbilical cord; signals the endometrium about forthcoming implantation; acts on receptor in mother's brain causing hyperemesis gravidarum, and seemingly promotes growth of fetal organs during pregnancy.Hyperglycosylated hCG functions to promote growth of cytotrophoblast cells and invasion by these cells, as occurs in implantation of pregnancy, and growth and invasion by choriocarcinoma cells. hCG free beta-subunit is produced by numerous non-trophoblastic malignancies of different primaries. The detection of free beta-subunit in these malignancies is generally considered a sign of poor prognosis. The free beta-subunit blocks apoptosis in cancer cells and promotes the growth and malignancy of the cancer. Pituitary hCG is a sulfated variant of hCG produced at low levels during the menstrual cycle. Pituitary hCG seems to mimic luteinizing hormone actions during the menstrual cycle.

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Section: Biological Function Of Free β-Subunitmentioning

confidence: 79%

Section: Biological Function Of Free β-Subunitmentioning

confidence: 96%

Biological functions of hCG and hCG-related molecules

Cole

2010

Reprod Biol Endocrinol

379

296

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“…They demonstrated the presence of the β subunit in metastatic malignancies in vivo [63] as well as in cultured cancer cells in vitro [64]. Other groups have confirmed this is cervical cancer and other cancers [65–67]. …”

Section: Biological Actionsmentioning

confidence: 99%

“…Both hyp-hCG and the β-subunit has been shown to act through the TGFβ receptor, and it is hypothesized that this occurs via similar pathways [6]. The application of hCG-β as a prognostic marker of poor prognosis in cancer is being examined in multiple tumor paradigms including cervical, vaginal, endometrial and bladder [65, 71–73]. These studies collectively indicate that the expression of the free β-subunit invokes a negative outcome in human malignancies.…”

Section: Biological Actionsmentioning

confidence: 99%

Extragonadal actions of chorionic gonadotropin

Banerjee

Fazleabas

2011

Rev Endocr Metab Disord

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The primary embryonic signal in primates is chorionic gonadotropin (CG, designated hCG in humans), that is classically associated with corpus luteum rescue and progesterone production. However, research over the past decade has revealed the presence of the hCG receptor in a variety of extragonadal tissues. Additionally, discoveries of the multiple variants of hCG, namely, native hCG, hyperglycosylated hCG (hyp-hCG) and the β-subunit of the hyperglycosylated hCG (hCG-free β) has established a role for extragonadal actions of hCG. For the initiation and maintenance of pregnancy, hCG mediates multiple placental, uterine and fetal functions. Some of these include development of syncytiotrophoblast cells, mitotic growth and differentiation of the endometrium, localized suppression of the maternal immune system, modulation of uterine morphology and gene expression and coordination of intricate signal transduction between the endometrium. Recurrent pregnancy loss, preeclampsia and endometriosis are associated with altered responses of hCG, all of which have a detrimental effect on pregnancy. A role for hyp-hCG in mediating the development of both trophoblastic and non-trophoblastic tumors has also been suggested. Other significant non-gonadal applications of hCG include predicting preeclampsia, determining the risk of Down’s syndrome and gestational trophoblastic disease, along with relaxing myometrial contractility and preventing recurrent miscarriages. Presence of hCG free-β in serum of cancer patients enables its usage as a diagnostic tumor marker. Thus, the extragonadal functions of hCG encompasses a wide spectrum of applications and is an open area for continued investigation.

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“…Slides were stained using standard immunohistochemistry (IHC) methods published elsewhere [32] . In brief, paraffin embedded tissue blocks were cut into 6μm sections, dewaxed and rehydrated through graded alcohol to water.…”

Section: Methodsmentioning

confidence: 99%