Tissue expression of human chorionic gonadotropin ? predicts outcome in colorectal cancer: A comparison with serum expression

Lundin, Mikael; Nordling, Stig; Lundin, Johan; Alfthan, Henrik; Stenman, Ulf‐Hǎkan; Haglund, Caj

doi:10.1002/1097-0215(20010120)95:1<18::aid-ijc1003>3.0.co;2-5

Cited by 37 publications

(29 citation statements)

References 35 publications

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“…So we conclude that hCG secreted by syncytiotrophoblastic cells might increase invasiveness of the extravillous trophoblast cells through down-regulating the expression of CD82 in DSCs. As is well known, several studies have reported the expression of hCG in a variety of cancers, including trophoblastic and testicular germ cell tumors, bladder cancer, colorectal cancer, ovarian cancer, lung cancer, pancreatic cancer, cervical cancer, prostate cancer, and breast cancer [41][42][43][44]. It is further reported that such cancers have poor prognosis and adverse survival rate.…”

Section: Discussionmentioning

confidence: 93%

The DSCs-Expressed CD82 Controls the Invasiveness of Trophoblast Cells via Integrinbeta1/MAPK/MAPK3/1 Signaling Pathway in Human First-Trimester Pregnancy1

Hou

Shao

et al. 2010

Biology of Reproduction

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CD82 is recognized as a wide-spectrum tumor metastasis suppressor that inhibits cancer cell motility and invasiveness. At the human maternal-fetal interface, the decidua is believed to effectively limit the inappropriate invasion of trophoblasts. Here we have found the transcription and translation of CD82 in decidual stromal cells (DSCs), whereas trophoblast cells do not express CD82. The in-cell Western analysis reveals attenuation of CD82 translation in DSCs by human chorionic gonadotropin (hCG), but not by estrogen or progesterone. It is demonstrated that silencing of CD82 by RNA interference increases integrinbeta1, decreases TIMP1 expression in DSCs, and promotes the invasion of the first-trimester human trophoblasts in the coculture. Moreover, U0126, or anti-integrinbeta1 neutralizing antibody, reverses the decreased TIMP1 expression and the increased invasiveness of trophoblast cells, and the antibody also inhibits the MAPK3/1 phosphorylation induced by CD82 silence. After transfection with CD82, the invasive index of BeWo cells decreases significantly with TIMP1 increase. The results above indicate that the DSCs-expressed CD82 up-regulates the expression of TIMP1 in an autocrine manner and inhibits the invasiveness of human first-trimester trophoblast cells partly through the integrinbeta1/MAPK/MAPK3/1 signaling pathway. Furthermore, we have found that the mRNA and protein level of CD82 in decidua of the miscarriage is significantly higher than that of the normal early pregnancy, which implies that the abnormal higher CD82 expression in decidua restricts appropriate invasion of trophoblasts that leads to early pregnancy wastage.

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Section: Discussionmentioning

confidence: 93%

The DSCs-Expressed CD82 Controls the Invasiveness of Trophoblast Cells via Integrinbeta1/MAPK/MAPK3/1 Signaling Pathway in Human First-Trimester Pregnancy1

Hou

Shao

et al. 2010

Biology of Reproduction

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“…Human chorionic gonadotropin bioactivity is dependent on glycosylation, the structure of which changes during early pregnancy trophoblast production [10][11][12]. In previous studies [13][14][15][16], hCG production has been confirmed as a common phenomenon associated with several different types of carcinomas. Some authors have reported that CGB or hCG is also produced at low levels by various normal human healthy tissues, particularly in the intestinal, urinary, and respiratory tracts [17][18][19][20] and in the fallopian tubes [21].…”

Section: Introductionmentioning

confidence: 99%

Epithelial Human Chorionic Gonadotropin Is Expressed and Produced in Human Secretory Endometrium During the Normal Menstrual Cycle1

Zimmermann

Ackermann

Alexander

2009

Biology of Reproduction

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The objective of this study was to determine whether beta human chorionic gonadotropin (hCG) (CGB) subunits and alpha hCG (CGA) subunits are expressed and the hCG dimer is produced in normal human cyclic endometrium. Endometrial specimens were collected for histological dating from women undergoing treatment in our division of human reproduction. RNA from normal secretory endometrium was extracted, and CGB and CGA gene expression was assessed by semiquantitative PCR. Adequate secretory endometrial specimens were homogenized using protease inhibitors. Proteins present in the supernatant were separated electrophoretically, and molecular hCG isoforms were detected by Western blot. The supernatant hCG concentrations were measured by ELISA. We characterized hCG and leukocytes in endometrial specimens by immunohistochemistry. Uterine flushing was performed to confirm endometrial hCG secretion into the uterine fluid. A full-length CGB mRNA encompassing the exon 1 promoter region and the structure exons 2 and 3 (including the C-terminal peptide) was expressed in normal secretory endometrial specimens (similar to CGA) during the early secretory phase of the menstrual cycle, up to an optimum at the midsecretory to late secretory phases. In homogenate supernatants obtained from normal secretory endometrium, hormone concentrations of dimeric hCG were approximately 5 mU per 10 mg of tissue, compared with considerably smaller concentrations of corresponding single free CGB subunit. Single chains of CGB, CGA, and dimeric molecular hCG isoforms were found in endometrial specimens by Western blot. Glandular endometrial hCG production is demonstrated immunohistochemically, with an increase toward the late secretory phase vs. the early secretory phase of the normal secretory menstrual cycle. However, glandular hCG release is diminished or absent in the dyssynchronous or missing endometrial secretory transformation. Endogenous endometrial hCG may be important for implantation and maintenance of pregnancy.

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“…13 Secretion of the free beta subunit of human chorionic gonadotropin has been reported in a number of nontrophoblastic epithelial malignancies. [3][4][5][6][7]11,[14][15][16][17] Tumor expression and/or secretion has been associated with more aggressive behavior and worse prognoses in many of these neoplasms. 15,[17][18][19] For example, beta-hCG expression by urothelial carcinomas correlates with advanced stage and grade.…”

Section: Discussionmentioning

confidence: 99%

Beta-Human Chorionic Gonadotropin Expression in Recurrent and Metastatic Giant Cell Tumors of Bone

et al. 2014

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Giant cell tumors of bone (GCTs) are generally benign, locally aggressive neoplasms that rarely metastasize. The beta subunit of human chorionic gonadotropin (beta-hCG) is expressed in syncytiotrophoblasts and several nongynecologic neoplasms but has not been described in GCT. At our institution, we observed cases of elevated beta-hCG in patients with GCT leading to diagnostic difficulty and in one case, concern for metastatic choriocarcinoma. This study aims to determine the frequency of beta-hCG expression in GCT and any relationship to clinical aggressiveness. We evaluated tissue expression of beta-hCG by immunohistochemistry with 58% of cases staining for beta-hCG. Additionally, 2 of 11 patients with available serum and/or urine beta-hCG measurements demonstrated elevated beta-hCG due to tumor. It is important to be aware of beta-hCG expression by GCT and the potential for elevated urine and serum beta-hCG levels in patients with GCT so as to avoid misdiagnosis of pregnancy or gestational trophoblastic disease.

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Tissue expression of human chorionic gonadotropin ? predicts outcome in colorectal cancer: A comparison with serum expression

Cited by 37 publications

References 35 publications

The DSCs-Expressed CD82 Controls the Invasiveness of Trophoblast Cells via Integrinbeta1/MAPK/MAPK3/1 Signaling Pathway in Human First-Trimester Pregnancy1

The DSCs-Expressed CD82 Controls the Invasiveness of Trophoblast Cells via Integrinbeta1/MAPK/MAPK3/1 Signaling Pathway in Human First-Trimester Pregnancy1

Epithelial Human Chorionic Gonadotropin Is Expressed and Produced in Human Secretory Endometrium During the Normal Menstrual Cycle1

Beta-Human Chorionic Gonadotropin Expression in Recurrent and Metastatic Giant Cell Tumors of Bone

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