Mitochondrial changes in endometrial carcinoma: Possible role in tumor diagnosis and prognosis (Review)

Cormio, Antonella; Cormio, Gennaro; Musicco, Clara; Sardanelli, Anna Maria; Gasparre, Giuseppe; Gadaleta, Maria Nicola

doi:10.3892/or.2014.3690

Cited by 20 publications

(22 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, our findings show a unique phenotypic difference between syngeneic tumors growing in Sparc -deficient mice; that is, the significant increase in mitochondrial number may reflect increased mitochondrial biogenesis concomitant with the upregulation of bioenergetic metabolic pathways. This is in accord with earlier studies that reported increased mitochondrial replication with changes in shape, size and number to influence metabolic remodeling of a myriad of physiological and pathological conditions including cancer [ 37 ].…”

Section: Discussionsupporting

confidence: 92%

SPARC Inhibits Metabolic Plasticity in Ovarian Cancer

Naczki

John

Patel

et al. 2018

Cancers

View full text Add to dashboard Cite

The tropism of ovarian cancer (OvCa) to the peritoneal cavity is implicated in widespread dissemination, suboptimal surgery, and poor prognosis. This tropism is influenced by stromal factors that are not only critical for the oncogenic and metastatic cascades, but also in the modulation of cancer cell metabolic plasticity to fulfill their high energy demands. In this respect, we investigated the role of Secreted Protein Acidic and Rich in Cysteine (SPARC) in metabolic plasticity of OvCa. We used a syngeneic model of OvCa in Sparc-deficient and proficient mice to gain comprehensive insight into the paracrine effect of stromal-SPARC in metabolic programming of OvCa in the peritoneal milieu. Metabolomic and transcriptomic profiling of micro-dissected syngeneic peritoneal tumors revealed that the absence of stromal-Sparc led to significant upregulation of the enzymes involved in glycolysis, TCA cycle, and mitochondrial electron transport chain (ETC), and their metabolic intermediates. Absence of stromal-Sparc increased reactive oxygen species and perturbed redox homeostasis. Recombinant SPARC exerted a dose-dependent inhibitory effect on glycolysis, mitochondrial respiration, ATP production and ROS generation. Comparative analysis with human tumors revealed that SPARC-regulated ETC-signature inversely correlated with SPARC transcripts. Targeting mitochondrial ETC by phenformin treatment of tumor-bearing Sparc-deficient and proficient mice mitigated the effect of SPARC-deficiency and significantly reduced tumor burden, ROS, and oxidative tissue damage in syngeneic tumors. In summary, our findings provide novel insights into the role of SPARC in regulating metabolic plasticity and bioenergetics in OvCa, and shines light on its potential therapeutic efficacy.

show abstract

Section: Discussionsupporting

confidence: 92%

SPARC Inhibits Metabolic Plasticity in Ovarian Cancer

Naczki

John

Patel

et al. 2018

Cancers

View full text Add to dashboard Cite

show abstract

“…Mutations, deletions, and changes in mtDNA copy number have been observed in cancers, particularly in response to therapy ( 36 – 38 ). However, the mechanisms and the clinical relevance of these phenomena remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer

Sansone

Savini

Kurelac

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

554

454

View full text Add to dashboard Cite

SignificanceIncreasing evidence suggests that extracellular vesicles (EVs) can transfer genetic material to recipient cells. However, the mechanism and role of this phenomenon are largely unknown. Here we have made a remarkable discovery: EVs can harbor the full mitochondrial genome. These extracellular vesicles can in turn transfer their mtDNA to cells with impaired metabolism, leading to restoration of metabolic activity. We determined that hormonal therapy induces oxidative phosphorylation-deficient breast cancer cells, which can be rescued via the transfer of mtDNA-laden extracellular vesicles. Horizontal transfer of mtDNA occurred in cancer stem-like cells and was associated with increased self-renewal potential of these cells, leading to resistance to hormonal therapy. We propose that mtDNA transfer occurs in human cancer via EVs.

show abstract

“…Ovarian, cervical and endometrial cancers are common gynecological malignancies, whose incidence are increasing (24)(25)(26). This is particularly evident in the case of ovarian cancer, which poses a serious threat to female health (25).…”

Section: Discussionmentioning

confidence: 99%

Olive oil exhibits osteoprotection in ovariectomized rats without estrogenic effects

Zheng

Huang

Zheng

et al. 2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. The present study was designed to evaluate the effect of olive oil on bone and uterus in ovariectomized rats. A total of 34 surgically ovariectomized or sham-operated virgin Sprague-Dawley rats were divided into four groups: i) Sham-operated control rats (sham group); ii) Ovariectomized rats (OVX group); iii) Olive oil-supplemented ovariectomized rats (olive group); and iv) Diethylstilbestrol-supplemented ovariectomized rats (E 2 group). At 12 weeks following left ventricular blood sacrificed to detect plasma estradiol (E 2 ), interleukin-1β (IL-1β) and IL-6 levels. Bone mineral density (BMD) of the lumbar spine was evaluated using dual-energy X-ray absorptiometry, and the left femur proximal 1/3 slices were observed using transmission electron microscopy. Uterine wet weight and the uterus index (ratio of uterine wet weight and body weight) were compared, and the uterine endometrium was observed using a light microscope. In the OVX group, serum E 2 was significantly lower and IL-1β and IL-6 levels were significantly higher compared with the sham group. By contrast, serum E 2 levels increased and IL-1β levels decreased in the olive group, but showed no significant difference compared with the sham group. The lumbar spine BMD in the olive group was increased compared with OVX group. Electron microscopy revealed sparse collagen fibers in the OVX group, with decreased density and multi-cavity, showing pathological features of osteoporosis. By contrast, the situation was improved in the E 2 and olive groups, in which organelles such as the rough endoplasmic reticulum, mitochondria and Golgi apparatus were visible and active. Compared with the sham group rats, the uterine wet weight and uterine index decreased in the OVX and olive groups; however, no statistically significant difference was observed in the E 2 group. Furthermore, endometrial hyperplasia was not observed in the olive group, which were apparently different from E 2 group. The present results suggest that olive oil can effectively reduce bone loss in ovariectomized rats, and with no or only mild effects on the uterine endothelium.

show abstract

Mitochondrial changes in endometrial carcinoma: Possible role in tumor diagnosis and prognosis (Review)

Cited by 20 publications

References 75 publications

SPARC Inhibits Metabolic Plasticity in Ovarian Cancer

SPARC Inhibits Metabolic Plasticity in Ovarian Cancer

Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer

Olive oil exhibits osteoprotection in ovariectomized rats without estrogenic effects

Contact Info

Product

Resources

About