Bone Metastasis from a Granulosa Cell Tumor of the Ovary

Dubuc-Lissoir, Josée; Berthiaume, Marie-Josée; Boubez, Ghassan; Nguyen, Thu Van; Allaire, Guy

doi:10.1006/gyno.2001.6367

Cited by 28 publications

(18 citation statements)

References 13 publications

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“…GCTs are able to metastasize to many organs [9]–[17], but the mechanisms underlying GCT metastasis are largely unknown. It seems likely that hormones and growth factors may contribute to GCT metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…However, these tumors have malignant potential and about 50% of cases are diagnosed with metastases [7]–[8]. There are reported cases of lung, liver, brain, bone, diaphragm, abdominal wall, pancreas and adrenal gland metastases from GCTs [9]–[17]. The mechanisms underlying GCT initiation, progression, recurrence and metastasis are unknown.…”

Section: Introductionmentioning

confidence: 99%

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Transforming Growth Factor Alpha (TGFα) Regulates Granulosa Cell Tumor (GCT) Cell Proliferation and Migration through Activation of Multiple Pathways

Wang

Jiang

et al. 2012

PLoS ONE

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Granulosa cell tumors (GCTs) are the most common ovarian estrogen producing tumors, leading to symptoms of excessive estrogen such as endometrial hyperplasia and endometrial adenocarcinoma. These tumors have malignant potential and often recur. The etiology of GCT is unknown. TGFα is a potent mitogen for many different cells. However, its function in GCT initiation, progression and metastasis has not been determined. The present study aims to determine whether TGFα plays a role in the growth of GCT cells. KGN cells, which are derived from an invasive GCT and have many features of normal granulosa cells, were used as the cellular model. Immunohistochemistry, Western blot and RT-PCR results showed that the ErbB family of receptors is expressed in human GCT tissues and GCT cell lines. RT-PCR results also indicated that TGFα and EGF are expressed in the human granulosa cells and the GCT cell lines, suggesting that TGFα might regulate GCT cell function in an autocrine/paracrine manner. TGFα stimulated KGN cell DNA synthesis, cell proliferation, cell viability, cell cycle progression, and cell migration. TGFα rapidly activated EGFR/PI3K/Akt and mTOR pathways, as indicated by rapid phosphorylation of Akt, TSC2, Rictor, mTOR, P70S6K and S6 proteins following TGFα treatment. TGFα also rapidly activated the EGFR/MEK/ERK pathway, and P38 MAPK pathways, as indicated by the rapid phosphorylation of EGFR, MEK, ERK1/2, P38, and CREB after TGFα treatment. Whereas TGFα triggered a transient activation of Akt, it induced a sustained activation of ERK1/2 in KGN cells. Long-term treatment of KGN cells with TGFα resulted in a significant increase in cyclin D2 and a decrease in p27/Kip1, two critical regulators of granulosa cell proliferation and granulosa cell tumorigenesis. In conclusion, TGFα, via multiple signaling pathways, regulates KGN cell proliferation and migration and may play an important role in the growth and metastasis of GCTs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transforming Growth Factor Alpha (TGFα) Regulates Granulosa Cell Tumor (GCT) Cell Proliferation and Migration through Activation of Multiple Pathways

Wang

Jiang

et al. 2012

PLoS ONE

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“…Wolf et al (4) showed a 43% response rate in patients with advanced stage or recurrent GCT who were treated with whole abdomen irradiation or pelvic irradiation. Some case reports describe the use of radiation treatment for isolated liver or bone recurrences (5, 6). However, there is no clear role for radiotherapy because of the lack of uniformity in staging and in treatment regimens.…”

Section: Discussionmentioning

confidence: 99%

GnRH Agonist Therapy in a Patient with Recurrent Ovarian Granulosa Cell Tumors

et al. 2009

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A 65-yr-old woman presented 17 yr status post-hysterectomy with bilateral ovarian salpingo-oophorectomy, attributable to ovarian cancer. She was admitted to our hospital, with multiple cystic liver masses and multiple large seeded masses in her abdomen and pelvic cavity. Histological examination of the pelvic masses demonstrated granulosa cell tumors. After two courses of systemic combination chemotherapy, with paclitaxel and carboplatin, the masses in the abdomen and pelvic cavity increased, and debulking surgery also failed because of peritoneal dissemination with severe adhesion. Finally, she underwent palliative radiotherapy for only the pelvic masses obstructing the urinary and GI tracts, and monthly hormonal therapy with a gonadotrophin-releasing hormone agonist; leuprorelin 3.75 mg IM. Subsequently, multiple masses beyond the range of the radiation as well as those within the radiotherapy field partially decreased. This partial response had been maintained for more than 8 months as of the last follow-up visit. Owing to its long and indolent course and the low metabolic rate of the tumors, advanced or recurrent granulosa cell tumor (GCT) requires treatment options beyond chemotherapy, surgery, and radiotherapy. Hormonal agents may provide another treatment option for advanced or recurrent GCT in those who are not candidates for surgery, chemotherapy, or radiotherapy.

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“…All documented metastases were intra-abdominal. Although bony metastases have been reported in ovarian granulosa cell tumour, it has never been reported in testicular granulosa cell tumour [6]. To the authors' knowledge, this is the fi rst case of granulosa cell tumour of the testes metastasising to bone.…”

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confidence: 78%

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Bone Metastasis from a Granulosa Cell Tumor of the Ovary

Cited by 28 publications

References 13 publications

Transforming Growth Factor Alpha (TGFα) Regulates Granulosa Cell Tumor (GCT) Cell Proliferation and Migration through Activation of Multiple Pathways

Transforming Growth Factor Alpha (TGFα) Regulates Granulosa Cell Tumor (GCT) Cell Proliferation and Migration through Activation of Multiple Pathways

GnRH Agonist Therapy in a Patient with Recurrent Ovarian Granulosa Cell Tumors

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