Loss of PTEN in Fallopian Tube Epithelium Results in Multicellular Tumor Spheroid Formation and Metastasis to the Ovary

Dean, Matthew; Jin, Vivian; Bergsten, Tova M.; Austin, Julia R.; Lantvit, Daniel D.; Russo, Angela; Burdette, Joanna E.

doi:10.3390/cancers11060884

Cited by 26 publications

(18 citation statements)

References 51 publications

(92 reference statements)

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“…The loss of PTEN functions impairs different key biological processes, ranging from inhibition of cell growth, proliferation, and migration, to promotion of apoptosis and tumor suppressor activity [23], findings that closely resemble our preclinical data. Relevant to our in vitro findings is also the observation that loss of PTEN in fallopian tube epithelium results in multicellular tumor spheroid formation and metastasis to ovary [35].…”

Section: Discussionsupporting

confidence: 75%

Clinical Value of lncRNA MEG3 in High-Grade Serous Ovarian Cancer

Buttarelli

Donato

Raspaglio

et al. 2020

Cancers

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Long non-coding RNAs (lncRNAs) are emerging as regulators in cancer development and progression, and aberrant lncRNA profiles have been reported in several cancers. Here, we evaluated the potential of using the maternally expressed gene 3 (MEG3) tissue level as a prognostic marker in high-grade serous ovarian cancer (HGSOC), the most common and deadliest gynecologic malignancy. To the aim of the study, we measured MEG3 transcript levels in 90 pre-treatment peritoneal biopsies. We also investigated MEG3 function in ovarian cancer biology. We found that high MEG3 expression was independently associated with better progression-free (p = 0.002) and overall survival (p = 0.01). In vitro and in vivo preclinical studies supported a role for MEG3 as a tumor suppressor in HGSOC, possibly through modulation of the phosphatase and tensin homologue (PTEN) network. Overall, results from this study demonstrated that decreased MEG3 is a hallmark for malignancy and tumor progression in HGSOC.

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Section: Discussionsupporting

confidence: 75%

Clinical Value of lncRNA MEG3 in High-Grade Serous Ovarian Cancer

Buttarelli

Donato

Raspaglio

et al. 2020

Cancers

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“…Human fallopian tube cells transformed in vitro produce tumours that are morphologically and genetically similar to HGSOC [15][16][17]. Genetically engineered mouse OC models containing mutations commonly found in HGSOC such as p53, PTEN, BRCA1, BRCA2, and Rb1 in tubal secretory cells have shown the phenotype of STIC formation and emergence of HGSOC [18][19][20]. Clinical studies have confirmed that the majority of women who undertook salpingo-oophorectomy due to the presence of BRCA1, 2 mutations had STICs in the fallopian tube.…”

Section: Different Origins Of Ocmentioning

confidence: 98%

Ovarian Cancer, Cancer Stem Cells and Current Treatment Strategies: A Potential Role of Magmas in the Current Treatment Methods

Ahmed

Kadife²,

Raza

et al. 2020

Cells

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Epithelial ovarian cancer (EOC) constitutes 90% of ovarian cancers (OC) and is the eighth most common cause of cancer-related death in women. The cancer histologically and genetically is very complex having a high degree of tumour heterogeneity. The pathogenic variability in OC causes significant impediments in effectively treating patients, resulting in a dismal prognosis. Disease progression is predominantly influenced by the peritoneal tumour microenvironment rather than properties of the tumor and is the major contributor to prognosis. Standard treatment of OC patients consists of debulking surgery, followed by chemotherapy, which in most cases end in recurrent chemoresistant disease. This review discusses the different origins of high-grade serous ovarian cancer (HGSOC), the major sub-type of EOC. Tumour heterogeneity, genetic/epigenetic changes, and cancer stem cells (CSC) in facilitating HGSOC progression and their contribution in the circumvention of therapy treatments are included. Several new treatment strategies are discussed including our preliminary proof of concept study describing the role of mitochondria-associated granulocyte macrophage colony-stimulating factor signaling protein (Magmas) in HGSOC and its unique potential role in chemotherapy-resistant disease. of 35have been observed in OC patients but not in patients with benign and borderline tumours, and this hypomethylation correlates with advanced-stage disease and poor prognosis [48,49]. A genome-wide methylation profiling of blood cells from healthy controls and age-matched untreated OC patients identified CpG methylation of 2714 cancer-related genes, of which 56% were hypomethylated [50]. Ovarian Cancer Stem CellsCellular heterogeneity associated with genetic and epigenetic changes in tumours are linked with the initiation and expansion of CSCs, a population of cells within the tumour, which initiate tumour growth through self-renewal and differentiation processes [51,52]. These cells are more adaptive to the changing tumour microenvironment and tend to be more resistant to treatment. CSCs are highly plastic and a few numbers of isolated CSCs have been shown to be responsible for tumorgenesis and are more chemotherapy and radiation resistant due to their dormant state and a high expression of drug efflux pumps [53,54]. As a result, CSCs are able to adapt to different tumour microenvironments and survive due to their efficient DNA repair mechanisms and their capacity to evade host immune surveillance [55][56][57]. These inherent properties of CSCs suggest an active role in tumour relapse and emphasize the need to develop effective targeted therapies to improve clinical outcomes in patients [51][52][53][54][55][56][57].Stem cells have been identified in ovaries and fallopian tubes [58,59]. These cells express proteins including aldehyde dehydrogenase family 1 A2 (ALDH1A2), homeobox protein NANOG, LIM homeobox protein 9 (LHX9) and frizzled-related protein 1 (SRFP1) and have been observed in OSE, CIC and fimbria [2,[58][59][60][61][62]. In a...

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“…Moreover, it was recently shown that the loss of PTEN allows the fallopian tube epithelia to form multicellular tumour spheroids, which survive better under ultra-low adhesion conditions, attach to the extracellular matrix exposed during ovulation, and colonize the ovary maybe contributing to seeding of the ovary in high grade serous OC patients [32].…”

Section: Ovarian Cancermentioning

confidence: 99%

PTEN and Gynecological Cancers

Nero

Ciccarone

Pietragalla

et al. 2019

Cancers

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PTEN is a tumour suppressor gene, and its loss of function is frequently observed in both heritable and sporadic cancers. It is involved in a great variety of biological processes, including maintenance of genomic stability, cell survival, migration, proliferation and metabolism. A better understanding of PTEN activity and regulation has therefore emerged as a subject of primary interest in cancer research. Gynaecological cancers are variously interested by PTEN deregulation and many perspective in terms of additional prognostic information and new therapeutic approaches can be explored. Here, we present the most significant findings on PTEN in gynaecological cancers (ovarian, endometrial, cervical, vulvar and uterine cancer) focusing on PTEN alterations incidence, biological role and clinical implications.

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Loss of PTEN in Fallopian Tube Epithelium Results in Multicellular Tumor Spheroid Formation and Metastasis to the Ovary

Cited by 26 publications

References 51 publications

Clinical Value of lncRNA MEG3 in High-Grade Serous Ovarian Cancer

Clinical Value of lncRNA MEG3 in High-Grade Serous Ovarian Cancer

Ovarian Cancer, Cancer Stem Cells and Current Treatment Strategies: A Potential Role of Magmas in the Current Treatment Methods

PTEN and Gynecological Cancers

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