Cell Adhesion in Ovarian Cancer

ElMasri, Wafic M.; Casagrande, Giovanna; Kimm, Daniel; Kohn, Elise C.

doi:10.1007/978-0-387-98094-2_14

Cited by 12 publications

(10 citation statements)

References 143 publications

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“…Based on randomized controlled trials, National Comprehensive Cancer Network panel members feel that surgery is the most appropriate option for patients with stage IB1 or IIA1 disease, whereas CCRT is the most appropriate option for those with stage IB2 or IIA2 disease [ 2 ]. The authors of the hitherto only study reporting the equivalent therapeutic efficacy and more favorable surgical outcomes of LRH versus ARH in patients with stage IB2 and IIA2 cervical cancer indicated that LRH was believed to be possible in all patients if the surgery was performed by an experienced surgeon [ 1 ].…”

Section: Discussionmentioning

confidence: 99%

“…Radical hysterectomy (RH) with pelvic and/or para-aortic lymph node (LN) dissection is a standard primary treatment for early-stage cervical cancer [ 2 ]. Although a laparoscopic approach is not yet incorporated into the treatment guidelines, laparoscopic radical hysterectomy (LRH) has become increasingly popular among gynecologic oncologists based on growing evidence supporting its safety and feasibility with equivalent oncologic outcomes of LRH compared with abdominal radical hysterectomy (ARH) for early-stage cervical cancer [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Matched-Case Comparisons in a Single Institution to Determine Critical Points for Inexperienced Surgeons’ Successful Performances of Laparoscopic Radical Hysterectomy versus Abdominal Radical Hysterectomy in Stage IA2-IIA Cervical Cancer

et al. 2015

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This is a retrospective study which aims to identify major determinants of successful laparoscopic radical hysterectomy (LRH) versus abdominal radical hysterectomy (ARH) performed by inexperienced surgeons for stage IA2-IIA cervical cancer. A total of 161 consecutive patients with stage IA2–IIA cervical cancer who underwent RH were grouped into 2 groups according to the surgeons’ experience with LRH: experienced surgeon versus inexperienced surgeon. After matching for age and risk factors, surgical and survival outcomes were compared. Experienced surgeon selected patients with earlier-stage and fewer risk factors for LRH than ARH, but inexperience surgeons did not. After matching, the vaginal tumor-free margin of LRH was shorter than that of ARH in experienced surgeon group (1.3 versus 1.7 cm, p=0.007); however, the vaginal tumor-free margin was longer than that of ARH in the inexperienced surgeon group (1.8 versus 1.3 cm, p=0.035). The postoperative hospital stay of LRH was shorter than that of ARH in experienced surgeon group (5.5 versus 7.7 days, p<0.001), but not different from that of ARH in the inexperienced surgeon group. Vaginal tumor-free margin >1.8 cm (OR 7.33, 95% CI 1.22–40.42), stage >IB1 (OR 8.83, 95% CI 1.51–51.73), and estimated blood loss >575 mL (OR 33.95, 95% CI 4.87–236.79) were independent risk factors for longer postoperative hospital stay in the inexperienced surgeon group. There was no difference of 5-year-profression-free survival of LRH patients between experienced surgeon and inexperienced surgeon groups after matching (55.1 versus 33.3%, p=0.391). Selection of earlier-stage disease and moderate vaginal tumor-free margin might be important for an inexperienced surgeon to successfully perform LRH with minimal complications in stage IA2–IIA cervical cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Matched-Case Comparisons in a Single Institution to Determine Critical Points for Inexperienced Surgeons’ Successful Performances of Laparoscopic Radical Hysterectomy versus Abdominal Radical Hysterectomy in Stage IA2-IIA Cervical Cancer

et al. 2015

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“…Cell adhesion molecules (CAMs) are involved in all phases of cancer progression [ 7 ]. CAMs are classically categorized into four groups: the cadherins, the integrins, the selectins, and the immunoglobulin-like CAMs (Ig-CAMs) [ 8 ]. Different kinds of CAMs are essential for cancer cells to maintain their survival and to alter their local microenvironment so that it is more feasible to sustain and promote tumor development [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

An epigenetic signature of adhesion molecules predicts poor prognosis of ovarian cancer patients

Chang

Liao²,

Wang³

et al. 2017

Oncotarget

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DNA methylation is a promising biomarker for cancer. The epigenetic effects of cell adhesion molecules may affect the therapeutic outcome and the present study examined their effects on survival in ovarian cancer. We integrated methylomics and genomics datasets in The Cancer Genome Atlas (n = 391) and identified 106 highly methylated adhesion-related genes in ovarian cancer tissues. Univariate analysis revealed the methylation status of eight genes related to progression-free survival. In multivariate Cox regression analysis, four highly methylated genes (CD97, CTNNA1, DLC1, HAPLN2) and three genes (LAMA4, LPP, MFAP4) with low methylation were significantly associated with poor progression-free survival. Low methylation of VTN was an independent poor prognostic factor for overall survival after adjustment for age and stage. Patients who carried any two of CTNNA1, DLC1 or MFAP4 were significantly associated with poor progression-free survival (hazard ratio: 1.59; 95% confidence interval: 1.23, 2.05). This prognostic methylation signature was validated in a methylomics dataset generated in our lab (n = 37, hazard ratio: 16.64; 95% confidence interval: 2.68, 103.14) and in another from the Australian Ovarian Cancer Study (n = 91, hazard ratio: 2.43; 95% confidence interval: 1.11, 5.36). Epigenetics of cell adhesion molecules is related to ovarian cancer prognosis. A more comprehensive methylomics of cell adhesion molecules is needed and may advance personalized treatment with adhesion molecule-related drugs.

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“…This is particularly relevant for ovarian cancer in view of the fact that tumor spheres commonly found in malignant ascites of ovarian cancer patients represent a significant impediment to efficacious treatment [ 8 ]. The observation that cancer stem/tumor-initiating cells can also be enriched by spheroids in suspension cultures further suggest spheroid cells may be associated with tumor aggressiveness [ 9 ]. Thus, cells cultured as 3D spheroids can be used as a tool to evaluate key metastatic events in the cascade.…”

Section: Introductionmentioning

confidence: 99%

“…Cadherins and integrins are major classes of cell surface receptors that mediate cell-cell and cell-matrix adhesion, respectively [ 7 ]. Cadherins, especially E-, N-, and P-cadherin have been implicated in the pathogenesis of ovarian cancer [ 8 ], and several integrins are expressed by ovarian tumor cells such as α2β1, α5β1, and αvβ3 [ 9 ]. However, the mechanistic basis of their crosstalk in ovarian cancer is not completely understood.…”

Section: Introductionmentioning

confidence: 99%

p70 S6 kinase drives ovarian cancer metastasis through multicellular spheroid-peritoneum interaction and P-cadherin/β1 integrin signaling activation

Yung

Chan

et al. 2014

Oncotarget

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Peritoneal dissemination as a manifestation of ovarian cancer is an adverse prognostic factor associated with poor clinical outcome, and is thus a potentially promising target for improved treatment. Sphere forming cells (multicellular spheroids) present in malignant ascites of patients with ovarian cancer represent a major impediment to effective treatment. p70 S6 kinase (p70S6K), which is a downstream effector of mammalian target of rapamycin, is frequently hyperactivated in human ovarian cancer. Here, we identified p70S6K as an important regulator for the seeding and successful colonization of ovarian cancer spheroids on the peritoneum. Furthermore, we provided evidence for the existence of a novel crosstalk between P-cadherin and β1 integrin, which was crucial for the high degree of specificity in cell adhesion. In particular, we demonstrated that the upregulation of mature β1 integrin occurred as a consequence of P-cadherin expression through the induction of the Golgi glycosyltransferase, ST6Gal-I, which mediated β1 integrin hypersialylation. Loss of p70S6K or targeting the P-cadherin/β1-integrin interplay could significantly attenuate the metastatic spread onto the peritoneum in vivo. These findings establish a new role for p70S6K in tumor spheroid-mesothelium communication in ovarian cancer and provide a preclinical rationale for targeting p70S6K as a new avenue for microenvironment-based therapeutic strategy.

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Cell Adhesion in Ovarian Cancer

Cited by 12 publications

References 143 publications

Matched-Case Comparisons in a Single Institution to Determine Critical Points for Inexperienced Surgeons’ Successful Performances of Laparoscopic Radical Hysterectomy versus Abdominal Radical Hysterectomy in Stage IA2-IIA Cervical Cancer

Matched-Case Comparisons in a Single Institution to Determine Critical Points for Inexperienced Surgeons’ Successful Performances of Laparoscopic Radical Hysterectomy versus Abdominal Radical Hysterectomy in Stage IA2-IIA Cervical Cancer

An epigenetic signature of adhesion molecules predicts poor prognosis of ovarian cancer patients

p70 S6 kinase drives ovarian cancer metastasis through multicellular spheroid-peritoneum interaction and P-cadherin/β1 integrin signaling activation

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