Orthotopic Model of Ovarian Cancer

Decio, Alessandra; Giavazzi, Raffaella

doi:10.1007/978-1-4939-3999-2_13

Cited by 7 publications

(11 citation statements)

References 36 publications

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“…Some scholars have verified that β-hCG dramatically promotes proliferation in nontrophoblastic solid tumors, such as bladder carcinoma, pituitary adenoma, choriocarcinoma and endometrial cancer [19][20][21]. In contrast, some scholars have found that β-hCG significantly suppresses breast cancer cell viability in vitro and inhibits tumor growth and attenuates tumor vessel formation in vivo [22]. In addition, β-hCG was confirmed to have no effect on the proliferation of colorectal cancer cells [23].…”

Section: Discussionmentioning

confidence: 99%

β-hCG promotes epithelial ovarian cancer metastasis through ERK/MMP2 signaling pathway

Wei

Gao

et al. 2018

Cell Cycle

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Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, with typically extensive intraperitoneal implantation leading to poor prognosis. Our previous study preliminarily demonstrated β-hCG can promote tumorigenesis in immortalized nontumorigenic ovarian epithelial cells. In this study, the roles and mechanisms of β-hCG in regulating EOC proliferation and metastasis were thoroughly explored. First, histologically, β-hCG was aberrantly overexpressed in human EOC metastatic tissues, and significantly correlated with FIGO stage, tumor size, differentiation, histologic grade and high grade serous ovarian carcinoma (HGSOC) (P < 0.05). However, serologically, β-hCG expression showed no significant difference between EOC and nonmalignant ovarian patients. Second, β-hCG was confirmed to have no significant effects on EOC proliferation in vitro and in vivo, while β-hCG upregulation was proven to promote migration and invasion ability in ES-2 and OVCAR-3 cells in vitro (P < 0.05), and β-hCG downregulation in SKOV3 cells had the opposite effect. Moreover, more invadopodia protrusions, mitochondria accumulations and cytoskeletal rearrangements were observed in β-hCG-overexpressing ES-2 cells, while β-hCG-depleted SKOV3 cells produced the opposite effect. Furthermore, β-hCG was confirmed to clearly facilitate intraperitoneal metastasis in nude mouse orthotopic ovarian xenograft models. Importantly, these effects of β-hCG were mediated by activation of the ERK/MMP2 signaling pathway, independently of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) presence, and inhibition the pathway with the p-ERK1/2 inhibitor SCH772984 significantly impaired the tumor-promoting effects induced by β-hCG. Collectively, these data provide new insight into the roles and mechanisms of β-hCG in regulating EOC metastasis through ERK/MMP2 signaling pathway and may become a new target for therapeutic intervention.

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Section: Discussionmentioning

confidence: 99%

β-hCG promotes epithelial ovarian cancer metastasis through ERK/MMP2 signaling pathway

Wei

Gao

et al. 2018

Cell Cycle

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“…Platinum-based chemotherapy (including cisplatin and carboplatin) is the first-line agent in the treatment of ovarian cancer. Metastases are the main reason for the high mortality in these patients [ 70 ]. Studies in model organisms have revealed a gradual increase in ovarian and pituitary let-7 expression, including let-7d, during ovarian development, suggesting a potential role of this microRNA in ovarian function [ 71 ].…”

Section: Let-7d and Ovarian Cancermentioning

confidence: 99%

The Role of microRNA Let-7d in Female Malignancies and Diseases of the Female Reproductive Tract

Santis¹,

Götte²

2021

IJMS

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microRNAs are small noncoding RNAs that regulate gene expression at the posttranscriptional level. Let-7d is a microRNA of the conserved let-7 family that is dysregulated in female malignancies including breast cancer, ovarian cancer, endometrial cancer, and cervical cancer. Moreover, a dysregulation is observed in endometriosis and pregnancy-associated diseases such as preeclampsia and fetal growth restriction. Let-7d expression is regulated by cytokines and steroids, involving transcriptional regulation by OCT4, MYC and p53, as well as posttranscriptional regulation via LIN28 and ADAR. By downregulating a wide range of relevant mRNA targets, let-7d affects cellular processes that drive disease progression such as cell proliferation, apoptosis (resistance), angiogenesis and immune cell function. In an oncological context, let-7d has a tumor-suppressive function, although some of its functions are context-dependent. Notably, its expression is associated with improved therapeutic responses to chemotherapy in breast and ovarian cancer. Studies in mouse models have furthermore revealed important roles in uterine development and function, with implications for obstetric diseases. Apart from a possible utility as a diagnostic blood-based biomarker, pharmacological modulation of let-7d emerges as a promising therapeutic concept in a variety of female disease conditions.

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“…IGROV1‐luc cells were injected orthotopically in the ovary (i.o. ), as previously described . Briefly, in anesthetized mice the skin was disinfected with Betadine and a 1–2 cm lateral midline skin incision performed to access the left ovary and exteriorize it and the oviduct.…”

Section: Methodsmentioning

confidence: 99%

“…), as previously described. 22 Briefly, in anesthetized mice the skin was disinfected with Betadine and a 1-2 cm lateral midline skin incision performed to access the left ovary and exteriorize it and the oviduct. 1 3 10 6 IGROV1-luc cells in 5-10 lL HBSS were injected under the bursa of the ovary, using a Hamilton syringe with a 26-gauge needle, followed by a slow removal of the needle to avoid spillage.…”

Section: What's New?mentioning

confidence: 99%

Tumor progression and metastatic dissemination in ovarian cancer after dose‐dense or conventional paclitaxel and cisplatin plus bevacizumab

Bizzaro

Falcetta

D'Agostini

et al. 2018

Intl Journal of Cancer

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The efficacy of therapeutic regimens incorporating weekly or every-3-weeks paclitaxel (PTX) for ovarian cancer is debated. We investigated the addition of bevacizumab in regimens of chemotherapy with different PTX doses and schedules in preclinical models. Treatments were cisplatin (DDP) with weekly PTX (conventional), or dose-dense-equi (every other day to the conventional cumulative dose), or dose-dense-high (total dose 1.5 times higher), with or without bevacizumab. Treatment efficacy was evaluated analyzing tumor growth in different time-windows in two patient-derived ovarian cancer xenografts with different sensitivity to cisplatin. Tumor progression, metastasis and survival were studied in ovarian cancer models growing orthotopically and disseminating in the mouse peritoneal cavity. Short-term effects on cell cycle, tumor cell proliferation/apoptosis and vasculature were evaluated by flow cytometry and immunohistochemistry. PTX dose-dense (with/without DDP) was superior to the conventional scheme in a dose-dependent manner; the high efficacy was confirmed by the lower ratio of tumor to normal cells. All schemes benefited from bevacizumab, which reduced tumor vessels. However, DDP/PTX dose-dense-high (only chemotherapy) was at least as active as DDP/PTX conventional plus bevacizumab. DDP/PTX dose-dense-high plus bevacizumab was the most effective in delaying tumor progression, though it did not prolong mouse survival and the continuous treatment with bevacizumab was associated with a malignant disease. These findings indicate that the effect of bevacizumab in combination with chemotherapy may depend on the schedule-dose of the treatment and help to explain the unclear benefits after bevacizumab.

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Orthotopic Model of Ovarian Cancer

Cited by 7 publications

References 36 publications

β-hCG promotes epithelial ovarian cancer metastasis through ERK/MMP2 signaling pathway

β-hCG promotes epithelial ovarian cancer metastasis through ERK/MMP2 signaling pathway

The Role of microRNA Let-7d in Female Malignancies and Diseases of the Female Reproductive Tract

Tumor progression and metastatic dissemination in ovarian cancer after dose‐dense or conventional paclitaxel and cisplatin plus bevacizumab

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