Role of Epithelial–Mesenchymal Plasticity in Pseudomyxoma Peritonei: Implications for Locoregional Treatments

Calabrò, Maria Luisa; Lazzari, Nayana; Rigotto, Giulia; Tonello, Marco; Sommariva, Antonio

doi:10.3390/ijms21239120

Cited by 9 publications

(9 citation statements)

References 143 publications

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“…Pseudomyxoma Peritonei (PMP) represents a unique form of PM with unique clinical challenges and underlying biology. We refer the reader to a focused recent review on PMP discussing the biology underlying PM formation and the consequences for treatment ( 75 ).…”

Section: Future Directionsmentioning

confidence: 99%

Peritoneal Metastases From Colorectal Cancer: Defining and Addressing the Challenges

2021

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The presence of peritoneal metastases (PM) in patients with colorectal cancer (CRC) is associated with an extremely poor prognosis. The diagnosis of PM is challenging, resulting in an underestimation of their true incidence. While surgery can be curative in a small percentage of patients, effective treatment for non-operable PM is lacking, and clinical and pre-clinical studies are relatively sparse. Here we have defined the major clinical challenges in the areas of risk assessment, detection, and treatment. Recent developments in the field include the application of organoid technology, which has generated highly relevant pre-clinical PM models, the application of diffusion-weighted MRI, which has greatly improved PM detection, and the design of small clinical proof-of-concept studies, which allows the efficient testing of new treatment strategies. Together, these developments set the stage for starting to address the clinical challenges. To help structure these efforts, a translational research framework is presented, in which clinical trial design is based on the insight gained from direct tissue analyses and pre-clinical (organoid) models derived from CRC patients with PM. This feed-forward approach, in which a thorough understanding of the disease drives innovation in its clinical management, has the potential to improve outcome in the years to come.

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Section: Future Directionsmentioning

confidence: 99%

Peritoneal Metastases From Colorectal Cancer: Defining and Addressing the Challenges

2021

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“…EMT plays a role in cancer development and progression by converting static epithelial cells into migratory and microenvironment-interacting mesenchymal cells, and by modulating the chemoresistance and stemness of tumor cells. Several findings highlighted that both EMT and MET contribute to cancer invasion and metastasis [ 31 ]. During EMT and MET, the expression profile of epithelial and mesenchymal markers E-cadherin, N-cadherin, Vimentin, cytokeratins, tight junction proteins, and β-catenin, are partly revealed [ 31 , 32 , 33 , 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Possible Action of Olaparib for Preventing Invasion of Oral Squamous Cell Carcinoma In Vitro and In Vivo

Nakamura

Fujihara

Kawaguchi

et al. 2022

IJMS

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Despite recent advances in treatment, the prognosis of oral cancer remains poor, and prevention of recurrence and metastasis is critical. Olaparib is a PARP1 inhibitor that blocks polyADP-ribosylation, which is involved in the epithelial–mesenchymal transition (EMT) characteristic of tumor recurrence. We explored the potential of olaparib in inhibiting cancer invasion in oral carcinoma using three oral cancer cell lines, HSC-2, Ca9-22, and SAS. Olaparib treatment markedly reduced their proliferation, migration, invasion, and adhesion. Furthermore, qRT-PCR revealed that olaparib inhibited the mRNA expression of markers associated with tumorigenesis and EMT, notably Ki67, Vimentin, β-catenin, MMP2, MMP9, p53, and integrin α2 and β1, while E-Cadherin was upregulated. In vivo analysis of tumor xenografts generated by injection of HSC-2 cells into the masseter muscles of mice demonstrated significant inhibition of tumorigenesis and bone invasion by olaparib compared with the control. This was associated with reduced expression of proteins involved in osteoclastogenesis, RANK and RANKL. Moreover, SNAIL and PARP1 were downregulated, while E-cadherin was increased, indicating the effect of olaparib on proteins associated with EMT in this model. Taken together, these findings confirm the effects of olaparib on EMT and bone invasion in oral carcinoma and suggest a new therapeutic strategy for this disease.

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“…Tumor invasion is a multifactor-driven process in which the synergistic interaction between tumor cells and stromal components is the driving force for tumor progression and metastasis. The tumor microenvironment is involved in tumorigenesis, progression, invasion, and metastasis by inducing stem cell-like characteristics and epithelial-mesenchymal transformation of tumor cells [ 17 ]. Therefore, the ratio of tumor and stroma can more accurately evaluate the biological behavior of tumors to a certain extent.…”

Section: Discussionmentioning

confidence: 99%

Tumor-stroma ratio as a new prognosticator for pseudomyxoma peritonei: a comprehensive clinicopathological and immunohistochemical study

Lin

et al. 2021

Diagn Pathol

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Background As a rare clinical tumor syndrome with an indolent clinical course and lack of pathognomonic symptoms, pseudomyxoma peritonei (PMP) is usually diagnosed at an advanced stage. In-depth pathological analysis is essential to assess tumor biological behaviors, assist treatment decision, and predict the clinical prognosis of PMP. The tumor-stroma ratio (TSR) is a promising prognostic parameter based on the tumor and stroma. This study explored the relationship between TSR and the pathological characteristics and prognosis of PMP. Methods PMP patients with complete data who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy were enrolled. The TSR of postoperative pathological images was quantitatively analyzed by Image-Pro Plus. Then the relationship between TSR and the clinicopathological characteristics, immunohistochemical characteristics and prognosis of PMP was analyzed. Results Among the 50 PMP patients included, there were 27 males (54.0%) and 23 females (46.0%), with a median age of 55 (range: 31–76) years. 25 (50.0%) patients were diagnosed with low-grade PMP (LG-PMP), and 25 (50.0%) were diagnosed with high-grade PMP (HG-PMP). There were 4 (8.0%) patients with vascular tumor emboli, 3 (6.0%) patients with nerve invasion, and 5 (10.0%) patients with lymph node metastasis. The immunohistochemical results showed that the Ki67 label index was < 25% in 18 cases (36.0%), 25 - 50% in 18 cases (36.0%) and > 50% in 14 cases (28.0%). The range of TSR was 2 - 24% (median: 8%). The cutoff value of TSR was 10% based on the receiver operating characteristic (ROC) curve and X-Tile analysis. There were 31 (62.0%) cases with TSR < 10% and 19 (38.0%) cases with TSR ≥ 10%. The TSR was closely related to histopathological type (P < 0.001) and Ki67 label index (P < 0.001). Univariate analysis showed that preoperative carcinoembryonic antigen (CEA), preoperative carbohydrate antigen 19–9, pathological type, vascular tumor emboli and TSR influenced the prognosis of PMP patients (P < 0.05). Multivariate analysis showed that preoperative CEA, vascular tumor emboli and the TSR were independent prognostic factors. Conclusions The TSR could be a new independent prognosticator for PMP.

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Role of Epithelial–Mesenchymal Plasticity in Pseudomyxoma Peritonei: Implications for Locoregional Treatments

Cited by 9 publications

References 143 publications

Peritoneal Metastases From Colorectal Cancer: Defining and Addressing the Challenges

Peritoneal Metastases From Colorectal Cancer: Defining and Addressing the Challenges

Possible Action of Olaparib for Preventing Invasion of Oral Squamous Cell Carcinoma In Vitro and In Vivo

Tumor-stroma ratio as a new prognosticator for pseudomyxoma peritonei: a comprehensive clinicopathological and immunohistochemical study

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