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Molecular Advances in Ovarian Cancer
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Molecular Advances in Ovarian Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 May 2024 | Viewed by 8749

Special Issue Editor

Dr. Te-Fu Chan

E-Mail Website
Guest Editor
1. Graduate Institute of Medicine, College of Medicine & Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
2. Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung 807377, Taiwan
Interests: high-risk pregnancies; perinatal medicine; genetic diagnosis; obstetrics and gynecology; endocrinology of reproduction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ovarian cancer is the most lethal gynecological malignancy in the world due to the lack of early detection tools and effective therapeutic intervention. Healthcare related to these has been an important issue and remains to be explored. Recent studies have identified that each histotype of ovarian cancer shows different molecular mechanisms of carcinogenesis. This special issue aim to collect paper focused on pathogenesis, tumor microenvironment in Ovarian cancer progression.

Dr. Te-Fu Chan
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pathogenesis
  • tumor microenvironment
  • ovarian cancer

Published Papers (7 papers)

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Research

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19 pages, 16710 KiB  
Article
Chondroitin Sulfate Proteoglycan 4 Provides New Treatment Approach to Preventing Peritoneal Dissemination in Ovarian Cancer
by Kaname Uno, Yoshihiro Koya, Masato Yoshihara, Shohei Iyoshi, Kazuhisa Kitami, Mai Sugiyama, Emiri Miyamoto, Kazumasa Mogi, Hiroki Fujimoto, Yoshihiko Yamakita, Xinhui Wang, Akihiro Nawa and Hiroaki Kajiyama
Int. J. Mol. Sci. 2024, 25(3), 1626; https://doi.org/10.3390/ijms25031626 - 28 Jan 2024
Viewed by 1043
Abstract
Most epithelial ovarian cancer (EOC) patients are diagnosed with peritoneal dissemination. Cellular interactions are an important aspect of EOC cells when they detach from the primary site of the ovary. However, the mechanism remains underexplored. Our study aimed to reveal the role of [...] Read more.
Most epithelial ovarian cancer (EOC) patients are diagnosed with peritoneal dissemination. Cellular interactions are an important aspect of EOC cells when they detach from the primary site of the ovary. However, the mechanism remains underexplored. Our study aimed to reveal the role of chondroitin sulfate proteoglycan 4 (CSPG4) in EOC with a major focus on cell–cell interactions. We examined the expression of CSPG4 in clinical samples and cell lines of EOC. The proliferation, migration, and invasion abilities of the CSPG4 knockdown cells were assessed. We also assessed the role of CSPG4 in spheroid formation and peritoneal metastasis in an in vivo model using sh-CSPG4 EOC cell lines. Of the clinical samples, 23 (44.2%) samples expressed CSPG4. CSPG4 was associated with a worse prognosis in patients with advanced EOC. Among the EOC cell lines, aggressive cell lines, including ES2, expressed CSPG4. When CSPG4 was knocked down using siRNA or shRNA, the cell proliferation, migration, and invasion abilities were significantly decreased compared to the control cells. Proteomic analyses showed changes in the expression of proteins related to the cell movement pathways. Spheroid formation was significantly inhibited when CSPG4 was inhibited. The number of nodules and the tumor burden of the omentum were significantly decreased in the sh-CSPG4 mouse models. In the peritoneal wash fluid from mice injected with sh-CSPG4 EOC cells, significantly fewer spheroids were present. Reduced CSPG4 expression was observed in lymphoid enhancer-binding factor 1-inhibited cells. CSPG4 is associated with aggressive features of EOC and poor prognosis. CSPG4 could be a new treatment target for blocking peritoneal metastasis by inhibiting spheroid formation. Full article
(This article belongs to the Special Issue Molecular Advances in Ovarian Cancer)
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19 pages, 8875 KiB  
Article
Human Fallopian Tube-Derived Organoids with TP53 and RAD51D Mutations Recapitulate an Early Stage High-Grade Serous Ovarian Cancer Phenotype In Vitro
by Yilin Dai, Jing Xu, Xiaofeng Gong, Jinsong Wei, Yi Gao, Ranran Chai, Chong Lu, Bing Zhao and Yu Kang
Int. J. Mol. Sci. 2024, 25(2), 886; https://doi.org/10.3390/ijms25020886 - 10 Jan 2024
Cited by 1 | Viewed by 1083
Abstract
RAD51D mutations have been implicated in the transformation of normal fallopian tube epithelial (FTE) cells into high-grade serous ovarian cancer (HGSOC), one of the most prevalent and aggressive gynecologic malignancies. Currently, no suitable model exists to elucidate the role of RAD51D in disease [...] Read more.
RAD51D mutations have been implicated in the transformation of normal fallopian tube epithelial (FTE) cells into high-grade serous ovarian cancer (HGSOC), one of the most prevalent and aggressive gynecologic malignancies. Currently, no suitable model exists to elucidate the role of RAD51D in disease initiation and progression. Here, we established organoids from primary human FTE and introduced TP53 as well as RAD51D knockdown to enable the exploration of their mutational impact on FTE lesion generation. We observed that TP53 deletion rescued the adverse effects of RAD51D deletion on the proliferation, stemness, senescence, and apoptosis of FTE organoids. RAD51D deletion impaired the homologous recombination (HR) function and induced G2/M phase arrest, whereas concurrent TP53 deletion mitigated G0/G1 phase arrest and boosted DNA replication when combined with RAD51D mutation. The co-deletion of TP53 and RAD51D downregulated cilia assembly, development, and motility, but upregulated multiple HGSOC-associated pathways, including the IL-17 signaling pathway. IL-17A treatment significantly improved cell viability. TP53 and RAD51D co-deleted organoids exhibited heightened sensitivity to platinum, poly-ADP ribose polymerase inhibitors (PARPi), and cell cycle-related medication. In summary, our research highlighted the use of FTE organoids with RAD51D mutations as an invaluable in vitro platform for the early detection of carcinogenesis, mechanistic exploration, and drug screening. Full article
(This article belongs to the Special Issue Molecular Advances in Ovarian Cancer)
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13 pages, 2605 KiB  
Article
Catecholamines Promote Ovarian Cancer Progression through Secretion of CXC-Chemokines
by Hyun Jung Kim, Ha Kyun Chang, Yul Min Lee and Kyun Heo
Int. J. Mol. Sci. 2023, 24(18), 14104; https://doi.org/10.3390/ijms241814104 - 14 Sep 2023
Viewed by 870
Abstract
Considerable evidence has accumulated in the last decade supporting the notion that chronic stress is closely related to the growth, metastasis, and angiogenesis of ovarian cancer. In this study, we analyzed the conditioned media in SKOV3 ovarian cancer cell lines treated with catecholamines [...] Read more.
Considerable evidence has accumulated in the last decade supporting the notion that chronic stress is closely related to the growth, metastasis, and angiogenesis of ovarian cancer. In this study, we analyzed the conditioned media in SKOV3 ovarian cancer cell lines treated with catecholamines to identify secreted proteins responding to chronic stress. Here, we observed that epinephrine and norepinephrine enhanced the secretion and mRNA expression of CXC-chemokines (CXCL1, 2, 3, and 8). Neutralizing antibodies to CXCL8 and CXCL8 receptor (CXCR2) inhibitors significantly reduced catecholamine-mediated invasion of SKOV3 cells. Finally, we found that the concentration of CXCL1 and CXCL8 in the plasma of ovarian cancer patients increased with stage progression. Taken together, these findings suggest that stress-related catecholamines may influence ovarian cancer progression through the secretion of CXC-chemokines. Full article
(This article belongs to the Special Issue Molecular Advances in Ovarian Cancer)
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Review

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22 pages, 1406 KiB  
Review
Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins
by Diana Luísa Almeida-Nunes, Ricardo Silvestre, Ricardo Jorge Dinis-Oliveira and Sara Ricardo
Int. J. Mol. Sci. 2024, 25(1), 323; https://doi.org/10.3390/ijms25010323 - 25 Dec 2023
Viewed by 1416
Abstract
Ovarian cancer metastization is accompanied by the development of malignant ascites, which are associated with poor prognosis. The acellular fraction of this ascitic fluid contains tumor-promoting soluble factors, bioactive lipids, cytokines, and extracellular vesicles, all of which communicate with the tumor cells within [...] Read more.
Ovarian cancer metastization is accompanied by the development of malignant ascites, which are associated with poor prognosis. The acellular fraction of this ascitic fluid contains tumor-promoting soluble factors, bioactive lipids, cytokines, and extracellular vesicles, all of which communicate with the tumor cells within this peritoneal fluid. Metabolomic profiling of ovarian cancer ascites has revealed significant differences in the pathways of fatty acids, cholesterol, glucose, and insulin. The proteins involved in these pathways promote tumor growth, resistance to chemotherapy, and immune evasion. Unveiling the key role of this liquid tumor microenvironment is crucial for discovering more efficient treatment options. This review focuses on the cholesterol and insulin pathways in ovarian cancer, identifying statins and metformin as viable treatment options when combined with standard chemotherapy. These findings are supported by clinical trials showing improved overall survival with these combinations. Additionally, statins and metformin are associated with the reversal of T-cell exhaustion, positioning these drugs as potential combinatory strategies to improve immunotherapy outcomes in ovarian cancer patients. Full article
(This article belongs to the Special Issue Molecular Advances in Ovarian Cancer)
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17 pages, 1198 KiB  
Review
Adipocyte Microenvironment in Ovarian Cancer: A Critical Contributor?
by Ana Duarte Mendes, Ana Rita Freitas, Rodrigo Vicente, Marina Vitorino, Marta Vaz Batista, Michelle Silva and Sofia Braga
Int. J. Mol. Sci. 2023, 24(23), 16589; https://doi.org/10.3390/ijms242316589 - 22 Nov 2023
Viewed by 974
Abstract
Ovarian cancer is one of the most common gynecological malignancies and has low survival rates. One of the main determinants of this unfavorable prognosis is the high rate of peritoneal metastasis at diagnosis, closely related to its morbidity and mortality. The mechanism underlying [...] Read more.
Ovarian cancer is one of the most common gynecological malignancies and has low survival rates. One of the main determinants of this unfavorable prognosis is the high rate of peritoneal metastasis at diagnosis, closely related to its morbidity and mortality. The mechanism underlying peritoneal carcinomatosis is not clearly defined, but a clear preference for omental spread has been described. Growing evidence suggests that adipose tissue plays a role in promoting cancer onset and progression. Moreover, obesity can lead to changes in the original functions of adipocytes, resulting in metabolic and inflammatory changes in the adipose tissue microenvironment, potentially increasing the risk of tumor growth. However, the specific roles of adipocytes in ovarian cancer have not yet been fully elucidated. Due to the undeniable link between obesity and cancer, the adipose tissue microenvironment could also present a promising therapeutic target that warrants further research. This review discusses the complex relationship between ovarian cancer and the adipose tissue microenvironment. Full article
(This article belongs to the Special Issue Molecular Advances in Ovarian Cancer)
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13 pages, 1318 KiB  
Review
Revisiting the Use of Normal Saline for Peritoneal Washing in Ovarian Cancer
by Hironari Akasaka and Honami Naora
Int. J. Mol. Sci. 2023, 24(22), 16449; https://doi.org/10.3390/ijms242216449 - 17 Nov 2023
Viewed by 1140
Abstract
The omentum is the predominant site of ovarian cancer metastasis, but it is difficult to remove the omentum in its entirety. There is a critical need for effective approaches that minimize the risk of colonization of preserved omental tissues by occult cancer cells. [...] Read more.
The omentum is the predominant site of ovarian cancer metastasis, but it is difficult to remove the omentum in its entirety. There is a critical need for effective approaches that minimize the risk of colonization of preserved omental tissues by occult cancer cells. Normal saline (0.9% sodium chloride) is commonly used to wash the peritoneal cavity during ovarian cancer surgery. The omentum has a prodigious ability to absorb fluid in the peritoneal cavity, but the impact of normal saline on the omentum is poorly understood. In this review article, we discuss why normal saline is not a biocompatible solution, drawing insights from clinical investigations of normal saline in fluid resuscitation and from the cytopathologic evaluation of peritoneal washings. We integrate these insights with the unique biology of the omentum and omental metastasis, highlighting the importance of considering the absorptive ability of the omentum when administering agents into the peritoneal cavity. Furthermore, we describe insights from preclinical studies regarding the mechanisms by which normal saline might render the omentum conducive for colonization by cancer cells. Importantly, we discuss the possibility that the risk of colonization of preserved omental tissues might be minimized by using balanced crystalloid solutions for peritoneal washing. Full article
(This article belongs to the Special Issue Molecular Advances in Ovarian Cancer)
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14 pages, 1855 KiB  
Review
Overview of Tumor Heterogeneity in High-Grade Serous Ovarian Cancers
by Eros Azzalini, Giorgio Stanta, Vincenzo Canzonieri and Serena Bonin
Int. J. Mol. Sci. 2023, 24(20), 15077; https://doi.org/10.3390/ijms242015077 - 11 Oct 2023
Viewed by 1523
Abstract
Ovarian cancers encompass a group of neoplasms originating from germinal tissues and exhibiting distinct clinical, pathological, and molecular features. Among these, epithelial ovarian cancers (EOCs) are the most prevalent, comprising five distinct tumor histotypes. Notably, high-grade serous ovarian cancers (HGSOCs) represent the majority, [...] Read more.
Ovarian cancers encompass a group of neoplasms originating from germinal tissues and exhibiting distinct clinical, pathological, and molecular features. Among these, epithelial ovarian cancers (EOCs) are the most prevalent, comprising five distinct tumor histotypes. Notably, high-grade serous ovarian cancers (HGSOCs) represent the majority, accounting for over 70% of EOC cases. Due to their silent and asymptomatic behavior, HGSOCs are generally diagnosed in advanced stages with an evolved and complex genomic state, characterized by high intratumor heterogeneity (ITH) due to chromosomal instability that distinguishes HGSOCs. Histologically, these cancers exhibit significant morphological diversity both within and between tumors. The histologic patterns associated with solid, endometrioid, and transitional (SET) and classic subtypes of HGSOCs offer prognostic insights and may indicate specific molecular profiles. The evolution of HGSOC from primary to metastasis is typically characterized by clonal ITH, involving shared or divergent mutations in neoplastic sub-clones within primary and metastatic sites. Disease progression and therapy resistance are also influenced by non-clonal ITH, related to interactions with the tumor microenvironment and further genomic changes. Notably, significant alterations occur in nonmalignant cells, including cancer-associated fibroblast and immune cells, during tumor progression. This review provides an overview of the complex nature of HGSOC, encompassing its various aspects of intratumor heterogeneity, histological patterns, and its dynamic evolution during progression and therapy resistance. Full article
(This article belongs to the Special Issue Molecular Advances in Ovarian Cancer)
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